Publications by authors named "A E Ebert"

492 Publications

MRI topography of lesions related to internuclear ophthalmoplegia in patients with multiple sclerosis or ischemic stroke.

J Neuroimaging 2021 Apr 1. Epub 2021 Apr 1.

Department of Neurology, Medical Faculty Mannheim and Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Mannheim, Germany.

Background And Purpose: Internuclear ophthalmoplegia is a dysfunction of conjugate eye movements, caused by lesions affecting the medial longitudinal fasciculus (MLF). Multiple sclerosis (MS) and ischemic stroke represent the most common pathophysiologies. While magnetic resonance imaging (MRI) allows for localizing lesions affecting the MLF, comprehensive comparative studies exploring potential different spatial characteristics of lesions affecting the MLF are missing until now.

Methods: We retrospectively investigated MRI examinations of 82 patients (40 patients with MS and 42 patients with ischemic stroke). For lesion localization, the brainstem was segmented into (1) ponto-medullary junction, (2) mid pons, (3) upper pons, and (4) mesencephalon.

Results: Corresponding lesions affecting the MLF were observed in 29/40 (72.5%) MS and 38/42 (90.5%) stroke patients. Compared to stroke patients, MS patients had significantly more lesions in multiple locations (P < .001). Stroke patients showed more lesions at the level of the mesencephalon (P < .001), while lesions at the level of the ponto-medullary junction, mid, and upper pons did not statistically differ between the groups.

Conclusion: Our results demonstrate that multiple lesions affecting the MLF make inflammatory-demyelination due to MS more likely, while lesion localization at the level of the mesencephalon favors ischemia.
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http://dx.doi.org/10.1111/jon.12847DOI Listing
April 2021

Integrated Ca flux and AFM force analysis in human iPSC-derived cardiomyocytes.

Biol Chem 2020 11 27;402(1):113-121. Epub 2020 Oct 27.

Heart Center, Department of Cardiology and Pneumology, University Medical Center, Göttingen University, Robert-Koch-Strasse 40, D-37075, Göttingen, Germany.

We developed a new approach for combined analysis of calcium (Ca) handling and beating forces in contractile cardiomyocytes. We employed human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from dilated cardiomyopathy (DCM) patients carrying an inherited mutation in the sarcomeric protein troponin T (TnT), and isogenic TnT-KO iPSC-CMs generated via CRISPR/Cas9 gene editing. In these cells, Ca handling as well as beating forces and -rates using single-cell atomic force microscopy (AFM) were assessed. We report impaired Ca handling and reduced contractile force in DCM iPSC-CMs compared to healthy WT controls. TnT-KO iPSC-CMs display no contractile force or Ca transients but generate Ca sparks. We apply our analysis strategy to Ca traces and AFM deflection recordings to reveal maximum rising rate, decay time, and duration of contraction with a multi-step background correction. Our method provides adaptive computing of signal peaks for different Ca flux or force levels in iPSC-CMs, as well as analysis of Ca sparks. Moreover, we report long-term measurements of contractile force dynamics on human iPSC-CMs. This approach enables deeper and more accurate profiling of disease-specific differences in cardiomyocyte contraction profiles using patient-derived iPSC-CMs.
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http://dx.doi.org/10.1515/hsz-2020-0212DOI Listing
November 2020

Plant chromatin, metabolism and development - an intricate crosstalk.

Curr Opin Plant Biol 2021 Jan 23;61:102002. Epub 2021 Jan 23.

Biology Centre, Czech Academy of Sciences, České Budějovice, Czech Republic; University of South Bohemia, Faculty of Science, České Budějovice, Czech Republic. Electronic address:

Chromatin structure influences DNA accessibility and underlying gene expression. Disturbances of chromatin structure often result in pleiotropic developmental phenotypes. Interactions between chromatin modifications and development have been the main focus of epigenetic studies. Recent years brought major advance in uncovering and understanding connections between chromatin organisation in the nucleus and metabolic processes that take place in the cytoplasm or other cellular compartments. Products of primary metabolism and cell redox states influence chromatin-modifying complexes, and chromatin modifiers in turn affect expression of metabolic genes. Current evidence indicates that complex interaction loops between these biological system layers exist. Applying interdisciplinary and holistic approaches will decipher causality and molecular mechanisms of the dynamic crosstalk between chromatin structure, metabolism and plant growth and development.
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http://dx.doi.org/10.1016/j.pbi.2021.102002DOI Listing
January 2021

Diffusely appearing white matter in multiple sclerosis: Insights from sodium (Na) MRI.

Mult Scler Relat Disord 2021 Jan 14;49:102752. Epub 2021 Jan 14.

Department of Neurology, Medical Faculty Mannheim and Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Theodor-Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany. Electronic address:

Background: In multiple sclerosis (MS), magnetic resonance imaging (MRI) frequently shows ill-defined areas with intermediate signal intensity between the normal appearing white matter (NAWM) and focal T2-hyperintense lesions, termed "diffusely appearing white matter" (DAWM). Even though several advanced MRI techniques have shown the potential to detect and quantify subtle commonly not visible microscopic tissue changes, to date only a few advanced MRI studies investigated DAWM changes in a quantitative manner. The aim of this study was to detect and quantify tissue abnormalities in the DAWM in comparison to focal lesions and the NAWM in MS patients by sodium (Na) MRI.

Methods: Na and conventional MRI were performed in 25 MS patients with DAWM (DAWM) and in 25 sex- and age matched MS patients without DAWM (DAWM), as well as in ten healthy controls (HC). Mean total sodium concentrations (TSC) were quantified in the DAWM, NAWM, normal appearing grey matter (NAGM) and in focal MS lesions.

Results: In MS DAWMand DAWM, TSC values were increased in the NAGM (DAWM: 44.61 ± 4.09 mM; DAWM: 45.37 ± 3.8 mM) and in the NAWM (DAWM: 39.85 ± 3.89 mM; DAWM: 39.82 ± 4.25 mM) compared to normal grey and white matter in HC (GM 40.87 ± 3.25 mM, WM 35.9 ± 1.81 mM; p < 0.05 for all comparisons). Interestingly, the DAWM showed similar sodium concentrations (39.32 ± 4.59 mM) to the NAWM (39.85 ± 3.89 mM), whereas TSC values in T1 hypointense (46.53 ± 7.87 mM) and T1 isointense (41.99 ± 6.10 mM) lesions were significantly higher than in the DAWM (p < 0.001 and 0.017 respectively).

Conclusion: Na MRI is confirmed as a sensitive marker of even subtle tissue abnormalities. DAWM sodium levels are increased and comparable to the abnormalities in NAWM, suggesting pathological changes less severe than in focal lesions comparable to what is expected in the NAWM.
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http://dx.doi.org/10.1016/j.msard.2021.102752DOI Listing
January 2021

Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis: a cross-sectional multicentre international study with experimental animal model.

Sci Rep 2021 Jan 14;11(1):1367. Epub 2021 Jan 14.

Institute for Translational Medicine, Medical School, Szentágothai Research Centre, University of Pécs, Pécs, Hungary.

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.
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http://dx.doi.org/10.1038/s41598-020-80532-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809468PMC
January 2021

Surgical versus clinical staging prior to primary chemoradiation in patients with cervical cancer FIGO stages IIB-IVA: oncologic results of a prospective randomized international multicenter (Uterus-11) intergroup study.

Int J Gynecol Cancer 2020 Dec;30(12):1855-1861

Department of Gynecology, University of Cologne, Koln, Germany.

Objective: Revised staging of patients with locally advanced cervical cancer is based on clinical examination, imaging, and potential surgical findings. A known limitation of imaging techniques is an appreciable rate of understaging. In contrast, surgical staging may provide more accurate information on lymph node involvement. The aim of this prospective study was to evaluate the impact of pre-treatment surgical staging, including removal of bulky lymph nodes, on disease-free survival in patients with locally advanced cervical cancer.

Methods: Uterus-11 was a prospective international multicenter study including patients with locally advanced cervical cancer who were randomized 1:1 to surgical staging (experimental arm) or clinical staging (control arm) followed by primary platinum-based chemoradiation. Patients with histologically proven squamous cell carcinoma, adenocarcinoma, or adenosquamous cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIB-IVA underwent gynecologic examination and pre-treatment imaging including abdominal computed tomography (CT) and/or abdominal magnetic resonance imaging (MRI). Patients had chest imaging (any of the following: X-ray, CT, or PET-CT). The primary endpoint was disease-free survival and the secondary endpoint was overall survival. An ad hoc analysis was performed after trial completion for cancer-specific survival. Randomization was conducted from February 2009 to August 2013.

Results: A total of 255 patients (surgical arm, n=130; clinical arm, n=125) with locally advanced cervical cancer were randomized. Of these, 240 patients were eligible for analysis. The two groups were comparable with respect to patient characteristics. The surgical approach was transperitoneal laparoscopy in most patients (96.6%). Laparoscopic staging led to upstaging in 39 of 120 (33%) patients. After a median follow-up of 90 months (range 1-123) in both arms, there was no difference in disease-free survival between the groups (p=0.084). For patients with FIGO stage IIB, surgical staging is superior to clinical staging with respect to disease-free survival (HR 0.51, 95% CI 0.30 to 0.86, p=0.011). In the post-hoc analysis, surgical staging was associated with better cancer-specific survival (HR 0.61, 95% CI 0.40 to 0.93, p=0.020).

Conclusion: Our study did not show a difference in disease-free survival between surgical and clinical staging in patients with locally advanced cervical cancer. There was a significant benefit in disease-free survival for patients with FIGO stage IIB and, in a post-hoc analysis, a cancer-specific survival benefit in favor of laparoscopic staging. The high risk of distant metastases in both arms emphasizes the need for further evaluation.
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http://dx.doi.org/10.1136/ijgc-2020-001973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788482PMC
December 2020

Plant Biodiversity and Genetic Resources Matter!

Plants (Basel) 2020 Dec 4;9(12). Epub 2020 Dec 4.

Alliance of Bioversity International and CIAT, Maccarese, 00054 Rome, Italy.

Plant biodiversity is the foundation of our present-day food supply (including functional food and medicine) and offers humankind multiple other benefits in terms of ecosystem functions and resilience to climate change, as well as other perturbations. This Special Issue on 'Plant Biodiversity and Genetic Resources' comprises 32 papers covering a wide array of aspects from the definition and identification of hotspots of wild and domesticated plant biodiversity to the specifics of conservation of genetic resources of crop genepools, including breeding and research materials, landraces and crop wild relatives which collectively are the pillars of modern plant breeding, as well as of localized breeding efforts by farmers and farming communities. The integration of genomics and phenomics into germplasm and genebank management enhances the value of crop germplasm conserved ex situ, and is likely to increase its utilization in plant breeding, but presents major challenges for data management and the sharing of this information with potential users. Furthermore, also a better integration of in situ and ex situ conservation efforts will contribute to a more effective conservation and certainly to a more sustainable and efficient utilization. Other aspects such as policy, access and benefit-sharing that directly impact the use of plant biodiversity and genetic resources, as well as balanced nutrition and enhanced resilience of production systems that depend on their increased use, are also being treated. The editorial concludes with six key messages on plant biodiversity, genetic erosion, genetic resources and plant breeding, agricultural diversification, conservation of agrobiodiversity, and the evolving role and importance of genebanks.
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http://dx.doi.org/10.3390/plants9121706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761872PMC
December 2020

Hindsight is 2020 vision: a characterisation of the global response to the COVID-19 pandemic.

BMC Public Health 2020 Dec 7;20(1):1868. Epub 2020 Dec 7.

School of Mathematical Sciences, Science and Engineering Faculty, Queensland University of Technology, Brisbane, Australia.

Background: The global impact of COVID-19 and the country-specific responses to the pandemic provide an unparalleled opportunity to learn about different patterns of the outbreak and interventions. We model the global pattern of reported COVID-19 cases during the primary response period, with the aim of learning from the past to prepare for the future.

Methods: Using Bayesian methods, we analyse the response to the COVID-19 outbreak for 158 countries for the period 22 January to 9 June 2020. This encompasses the period in which many countries imposed a variety of response measures and initial relaxation strategies. Instead of modelling specific intervention types and timings for each country explicitly, we adopt a stochastic epidemiological model including a feedback mechanism on virus transmission to capture complex nonlinear dynamics arising from continuous changes in community behaviour in response to rising case numbers. We analyse the overall effect of interventions and community responses across diverse regions. This approach mitigates explicit consideration of issues such as period of infectivity and public adherence to government restrictions.

Results: Countries with the largest cumulative case tallies are characterised by a delayed response, whereas countries that avoid substantial community transmission during the period of study responded quickly. Countries that recovered rapidly also have a higher case identification rate and small numbers of undocumented community transmission at the early stages of the outbreak. We also demonstrate that uncertainty in numbers of undocumented infections dramatically impacts the risk of multiple waves. Our approach is also effective at pre-empting potential flare-ups.

Conclusions: We demonstrate the utility of modelling to interpret community behaviour in the early epidemic stages. Two lessons learnt that are important for the future are: i) countries that imposed strict containment measures early in the epidemic fared better with respect to numbers of reported cases; and ii) broader testing is required early in the epidemic to understand the magnitude of undocumented infections and recover rapidly. We conclude that clear patterns of containment are essential prior to relaxation of restrictions and show that modelling can provide insights to this end.
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http://dx.doi.org/10.1186/s12889-020-09972-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719727PMC
December 2020

Venous Diameter Changes in Chronic Active Multiple Sclerosis Lesions.

J Neuroimaging 2021 Mar 3;31(2):394-400. Epub 2020 Dec 3.

Department of Neurology, Medical Faculty Mannheim and Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Mannheim, Germany.

Background And Purpose: To investigate the temporal evolution of venous diameter in chronic active and nonenhancing shrinking multiple sclerosis (MS) lesions in a longitudinal magnetic resonance imaging (MRI) study including susceptibility-weighted images (SWI).

Methods: We compared the venous diameter in chronic active and nonenhancing shrinking lesions to the venous diameter in nonenhancing stable lesions on two 3 T MRI data sets obtained 12 months apart. Chronic active and nonenhancing shrinking lesions were identified by Voxel-Guided Morphometry. Coregistered, overlaid fluid-attenuated inversion recovery/SWI were analyzed for the presence of a central vein. Quantitative calculation of the venous diameter for each time point was performed on the reconstructed veins.

Results: Sixty-two relapsing-remitting MS patients (50 women; mean age: 36 ± 11 years; mean disease duration: 4 ± 7 years) were included in the study. Overall, we identified 222 chronic MS lesions (48 chronic active, 48 shrinking, 126 stable) with a corresponding intralesional central vein. On baseline MRI, the mean venous diameter did not statistically differ between all subgroups, whereas on follow-up MRI, the mean intralesional venous diameter was smaller in chronic active (0.92 ± 0.15 mm) and shrinking lesions (0.90 ± 0.19 mm) compared to stable lesions (1.10 ± 0.18 mm; P < .001).

Conclusion: Our findings demonstrate venous narrowing in chronic active and nonenhancing shrinking MS lesions. The smaller diameter of intralesional veins during follow up in these lesions may reflect structural, degenerative, and metabolic changes due to chronic inflammation, (perivascular) fibrosis, collagenous thickening, and increased levels of oxygenated hemoglobin.
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http://dx.doi.org/10.1111/jon.12818DOI Listing
March 2021

Decreased admissions and change in arrival mode in patients with cerebrovascular events during the first surge of the COVID-19 pandemic.

Neurol Res Pract 2020 16;2:47. Epub 2020 Nov 16.

Department of Neurology and Mannheim Center for Translational Neuroscience, Heidelberg University, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany.

Background And Purpose: Investigating clinical characteristics of patients presenting with cerebrovascular events during the pandemic may provide valuable insight into further understanding the phenomenon of decreased stroke admissions during the COVID-19 pandemic.

Method: Data of patients presenting with a cerebrovascular event to the emergency department during weeks 12-17/2020 were compared to data from the respective weeks in 2019.

Results: A significant reduction in the number of admissions by 35.9% ( = 0.005) was observed during the COVID-19 epoch. In addition, significantly more patients arrived by ambulance during the COVID-19 epoch (2019: 75.7%, 2020: 94.2%;  = 0.001).

Conclusion: Our data may have implications as to how campaigns raising awareness for serious medical conditions in the context of the pandemic should be framed.
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http://dx.doi.org/10.1186/s42466-020-00094-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668014PMC
November 2020

Human-induced pluripotent stem cells as models for rare cardiovascular diseases: from evidence-based medicine to precision medicine.

Pflugers Arch 2020 Nov 18. Epub 2020 Nov 18.

Key Laboratory of combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Rare cardiovascular diseases (RCDs) refer to those cardiovascular diseases that display a low prevalence as well as morbidity. Due to the vast variety of underlying genetic mutations and the relatively low patient population, RCDs present additional challenges for diagnosis. Precision medicine may offer opportunities for designing patient-specific therapies in particular for carriers of variants with undetermined significance. Moreover, precision medicine strategies provide benefit to patients with "common" symptoms but carry in rare genetic variants. Induced pluripotent stem cells (iPSCs) present a state-of-the-art precision medicine approach which recently made contributions to the study of RCDs via patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). Human iPSC-CMs are derived from a patient's somatic cells and thus recapitulate a personalized genomics background, serving as patient-specific disease models. In light of these advantages, iPSC-CMs evolved as an effective tool for modeling cardiac disease phenotypes and accurately evaluating the toxicity of potential therapeutic compounds. This review covers approaches for studying RCDs and iPSC-CM models generated so far for different RCDs, such as long QT syndrome (LQT), short QT syndrome (SQT), Brugada syndrome (BrS), arrhythmogenic right ventricular cardiomyopathy (ARVC), and other rare diseases accomplished by cardiac-related syndromes like Fabry disease (FD) and Marfan syndrome (MFS). This overview aims to aid better understanding of the utility of iPSC-CM models, their various features, and future prospects.
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http://dx.doi.org/10.1007/s00424-020-02486-yDOI Listing
November 2020

Emotional Well-being During the First Four Months of COVID-19 in the United States.

J Adult Dev 2020 Oct 23:1-8. Epub 2020 Oct 23.

Department of Psychology, West Virginia University, 53 Campus Drive, Morgantown, WV 26506-6040 USA.

Relative to younger adults, older adults have demonstrated higher emotional well-being in the face of the threats of COVID-19 (e.g., Bruine de Bruin in J Gerontol 10.1093/geronb/gbaa074, 2020) and other events (Bonanno and Diminich in J Child Psychol Psychiatry 54:378-401, 2013). Thus, we predicted that levels of well-being would show minimal change in the first 4 months of COVID-19, with older adults faring better than younger adults. Adults ( = 325, age = 39.7, SD = 12.3) were surveyed before the pandemic began and at four additional time points throughout the first 4 months of the COVID-19 outbreak in the United States. Participants provided demographic information and completed measures of positive and negative affect. Latent growth curves were used to analyze changes in well-being over time, with age as a covariate. There was a significant linear increase in positive affect. Older age was positively associated with initial levels, but age was not associated with the slope. There was a significant curvilinear pattern in negative affect, with an initial increase, which, although remaining elevated, exhibited slow decreases over time. Age was significantly and negatively associated with initial negative affect, but age did not influence the shape or rate of change over time. We detected changes in both positive affect and negative affect during the first 4 months of COVID-19. The magnitude of these changes suggests that the stress of COVID-19 does not lead to an immediate decrease in well-being. Moreover, although older adults showed higher positive affect and lower negative affect relative to other adults, age differences in the trajectory of change did not emerge. Delayed and long-term effects on well-being and whether those effects are age-invariant should be examined over longer periods of time.
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http://dx.doi.org/10.1007/s10804-020-09365-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584310PMC
October 2020

Altered interoception in patients with borderline personality disorder: a study using heartbeat-evoked potentials.

Borderline Personal Disord Emot Dysregul 2020 22;7:24. Epub 2020 Oct 22.

LWL University Hospital, Department of Psychiatry, Psychotherapy and Preventive Medicine, Division of Social Neuropsychiatry and Evolutionary Medicine, Ruhr University Bochum, Alexandrinenstr. 1, D-44791 Bochum, Germany.

Background: Patients with borderline personality disorder (BPD) experience difficulties in emotional awareness (alexithymia), and often develop dissociative symptoms, which may reflect broader deficits in interoceptive awareness. Whether this is associated with alterations in cortical processing of interoception is currently unknown.

Methods: We utilized an electrophysiological marker of interoception, i.e. heartbeat-evoked potentials (HEP), and examined its relationship with electrocardiographic correlates of autonomic nervous system (ANS) functioning (heart rate variability), and with self-report measures of alexithymia, dissociation and borderline symptom severity in patients with BPD.

Results: Individuals with BPD had higher HEP amplitudes over frontal electrodes compared to healthy controls. Sympathetic ANS activity was greater in BPD patients than in controls. Across groups, HEP amplitudes were associated with parasympathetic activity over central electrodes and correlated with alexithymia over frontal electrodes.

Conclusions: These findings support the idea that difficulties in emotional awareness in BPD are reflected in altered frontal electrophysiological markers of interception. Therefore, emotional awareness can be understood as failures of modulation between interoceptive and exteroceptive attention. Future research may aim to investigate whether altered interoception and its electrophysiological correlates are malleable by therapeutic intervention.
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http://dx.doi.org/10.1186/s40479-020-00139-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579937PMC
October 2020

[7/m with nighttime bed wetting : Preparation for the medical specialist examination: case 4].

Authors:
U Necknig A Ebert

Urologe A 2020 Dec;59(Suppl 2):180-184

Sektion Kinderurologie, Urologische Universitätsklinik Ulm, Ulm, Deutschland.

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http://dx.doi.org/10.1007/s00120-020-01361-zDOI Listing
December 2020

Negative Impact of the COVID-19 Pandemic on Admissions for Intracranial Hemorrhage.

Front Neurol 2020 18;11:584522. Epub 2020 Sep 18.

Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Heidelberg, Germany.

The COVID-19 pandemic has seriously impacted healthcare systems worldwide. Admissions for various non-COVID-19 emergencies have significantly decreased. We sought to determine the impact of COVID-19 on admissions for intracranial hemorrhage to a German University Hospital emergency department. In a retrospective analysis of admissions to the emergency department of the University Hospital Mannheim from January to June 2020 and the corresponding time period in 2019, all patients admitted for either traumatic or non-traumatic intracranial hemorrhage were evaluated. Poisson regression was performed to analyze changes in admission rates as a function of year, epoch (COVID-19-epoch, March to April 2020 and corresponding months 2019; non-COVID-19-epoch, January to February and May to June 2019/2020) and the interaction of year and epoch (reflecting the impact of the pandemic and subsequent lockdown measures). Overall, 320 patients were included in the study. During the COVID-19-epoch, admission rates for spontaneous intracranial hemorrhage decreased significantly by 42.1% (RR 0.579, = 0.002, 95% confidence interval 0.410-0.818). Likewise, admission rates for traumatic intracranial hemorrhage decreased significantly by 53.7% [RR = 0.463, < 0.001, 95% confidence interval (CI) 0.358-0.599]. The decrease of spontaneous intracranial hemorrhages may be a consequence of underutilization of the healthcare system whereas decreasing rates of traumatic intracranial hemorrhage admissions may predominantly reflect a decrease in true incidence rates due to lockdown measures with restricted mobility. Raising patient awareness to seek emergency healthcare for acute neurological deficits during lockdown measures is important to ensure appropriate emergency care for patients with intracranial hemorrhage.
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http://dx.doi.org/10.3389/fneur.2020.584522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530817PMC
September 2020

Changes in Demographic and Diagnostic Spectra of Patients with Neurological Symptoms Presenting to an Emergency Department During the COVID-19 Pandemic: A Retrospective Cohort Study.

Neuropsychiatr Dis Treat 2020 30;16:2221-2227. Epub 2020 Sep 30.

Department of Neurology, Medical Faculty Mannheim and Mannheim Center for Translational Neurosciences (MCTN), Heidelberg University, Mannheim, Germany.

Objective: To analyse the characteristics of patients with neurological complaints seeking evaluation in an interdisciplinary emergency department (ED) during the rise of the COVID-19 pandemic in Germany.

Methods: In this retrospective study, data on the number of ED presentations due to neurological complaints in weeks 1-15/2020 were collected. In addition, hospital chart data of patients referred for neurological evaluation during weeks 12-15/2020 when the pandemic began impacting on public life in Germany were analysed regarding demographic information, chief complaints, modes of presentation and disposition and ED discharge diagnosis. Both data sets were compared to respective periods from 2017.

Results: During the surge of COVID-19, we found a significant decrease of the total number of neurological ED patients by 47.6%. Comparing weeks 12-15 of 2017 and 2020, we found a decrease in the number of patients of <30 years (p<0.001) and an increase of those 70 years (p<0.001). A higher proportion of patients were admitted to escalated care (p=0.03), and fewer patients were discharged against medical advice (p<0.001). In addition, the ratio of less acute diagnoses (eg, benign headaches) declined significantly.

Conclusion: Our findings suggest that the pandemic has contributed to a - potentially transient - reframing of laypeople's perception of urgency and necessity for emergency presentation. The establishment and promotion of health-care structures and services like telemedical consultations and the creation of safe ED environments will be essential to enable adequate delivery of care in potential future waves of the pandemic.
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http://dx.doi.org/10.2147/NDT.S273913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535112PMC
September 2020

Spread of Terbinafine-Resistant Type VIII (India) in Germany-"The Tip of the Iceberg?"

J Fungi (Basel) 2020 Oct 5;6(4). Epub 2020 Oct 5.

Labor für Medizinische Mikrobiologie, 04571 Rötha OT Mölbis, Germany.

Chronic recalcitrant dermatophytoses, due to (.) Type VIII are on the rise in India and are noteworthy for their predominance. It would not be wrong to assume that travel and migration would be responsible for the spread of . Type VIII from India, with many strains resistant to terbinafine, to other parts of the world. From September 2016 until March 2020, a total of 29 strains of . Type VIII (India) were isolated. All patients were residents of Germany: 12 females, 15 males and the gender of the remaining two was not assignable. Patients originated from India (11), Pakistan (two), Bangladesh (one), Iraq (two), Bahrain (one), Libya (one) and other unspecified countries (10). At least two patients were German-born residents. Most samples (21) were collected in 2019 and 2020. All 29 . isolates were sequenced (internal transcribed spacer (ITS) and translation elongation factor 1-α gene (TEF1-α)). All were identified as genotype VIII (India) of . . In vitro resistance testing revealed 13/29 strains (45%) to be terbinafine-resistant with minimum inhibitory concentration (MIC) breakpoints ≥0.2 µg/mL. The remaining 16 strains (55%) were terbinafine-sensitive. Point mutation analysis revealed that 10/13 resistant strains exhibited PheLeu amino acid substitution of squalene epoxidase (SQLE), indicative for in vitro resistance to terbinafine. Two resistant strains showed combined PheLeu and AlaThr amino acid substitutions, and one strain a single LeuPhe amino acid substitution. Out of 16 terbinafine-sensitive strains, in eight AlaThr, and in one AlaThr +, new Val Ile amino acid substitutions were detected. Resistance to both itraconazole and voriconazole was observed in three out of 13 analyzed strains. Treatment included topical ciclopirox olamine plus topical miconazole or sertaconazole. Oral itraconazole 200 mg twice daily for four to eight weeks was found to be adequate. Terbinafine-resistant . Type VIII are being increasingly isolated. In Germany, transmission of . Type VIII from the Indian subcontinent to Europe should be viewed as a significant public health issue.
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http://dx.doi.org/10.3390/jof6040207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712673PMC
October 2020

Psychometric properties of the German version of the Forms of Self-Criticizing/Attacking and Self-Reassuring Scale (FSCRS).

Psychol Assess 2021 Jan 28;33(1):97-110. Epub 2020 Sep 28.

Department of Public Health and Health Education, University of Education of Freiburg.

Self-criticism is significantly associated with a variety of mental health difficulties affecting vulnerability, presentation, progress, and recovery. In contrast, self-reassurance is associated with good mental health, psychological well-being, and beneficial physiological processes. The 22-item Forms of Self-Criticizing/Attacking and Self-Reassuring Scale (FSCRS) is an internationally used self-report questionnaire for measuring manifestation and changes in different types of self-criticism and self-reassurance. It has been shown to be a valid and reliable measure in clinical and nonclinical samples. In the present study, a German translation of the FSCRS and its 3 subscales (hated self, inadequate self, reassured self) was provided, and the factor structure and psychometric properties were examined in 415 participants from 4 different population samples: (a) a sample from the general population, (b) a sample of psychiatric residential and outpatients, (c) a clinical sample of residential and outpatients with a primary diagnosis of borderline personality disorder (BPD), and (d) a sample of healthy control participants. Results from confirmatory factor analysis favored a 3-factor solution of the German FSCRS. Furthermore, findings indicate that the German version of the FSCRS and its subscales had good to excellent internal consistencies. Convergent validity was good for all 3 subscales as shown by medium to large correlations with established measures of self-criticism, self-compassion, self-esteem, satisfaction with life, symptoms of depression and anxiety, and secure attachment styles. Additionally, the 3 FSCRS subscales discriminated significantly between the clinical and nonclinical samples, with the BPD sample demonstrating significantly higher levels than the other samples on the hated self subscale. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/pas0000956DOI Listing
January 2021

Susceptibility-Weighted 3T MRI of the Swallow Tail Sign in Multiple Sclerosis: A Case Control Study.

J Neuroimaging 2020 11 28;30(6):766-768. Epub 2020 Aug 28.

Department of Neurology, Medical Faculty Mannheim and Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Mannheim, Germany.

Background And Purpose: The swallow tail sign describes the physiological appearance of nigrosome-1 within the substantia nigra on high-resolution transverse susceptibility-weighted imaging (SWI). Previous studies demonstrated its absence in Parkinson's disease due to increasing iron content. In multiple sclerosis (MS), increased iron accumulation can be found in the brain tissue including the substantia nigra.

Methods: We investigated the swallow tail sign on high-resolution SWI MRI in 46 MS and 23 age- and sex-matched controls.

Results: MS patients demonstrated significantly more often an abnormal swallow tail sign (28/46; 60%) compared to controls (4/23; 17%; P = .001). In MS patients, we found no correlation between an abnormal swallow tail sign and age, disease duration or Expanded Disability Status Scale scores.

Conclusion: The finding of an abnormal swallow tail sign in MS patients may provide an additional imaging marker even in early MS development.
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http://dx.doi.org/10.1111/jon.12775DOI Listing
November 2020

Is Involved in Urinary Tract and Urorectal Development.

Front Cell Dev Biol 2020 7;8:567. Epub 2020 Aug 7.

Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.

Previous studies in developing and zebrafish reported that the phosphate transporter is expressed in pronephric kidneys. The recent identification of as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog . This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest is involved in urinary tract and urorectal development and implicate as a disease-gene for BEEC.
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http://dx.doi.org/10.3389/fcell.2020.00567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426641PMC
August 2020

Psychometric properties of the German version of the fears of compassion scales.

Clin Psychol Psychother 2021 Jan 18;28(1):137-149. Epub 2020 Aug 18.

Institute of Psychiatric and Psychosomatic Psychotherapy, Central Institute of Mental Health Mannheim, Mannheim, Germany.

The cultivation of compassion is associated with beneficial effects on physical and psychological health, satisfaction with life and social relationships. However, some individuals, especially those high in psychopathological symptoms or those with particular disorders such as borderline personality disorder (BPD) may demonstrate pronounced fears of engagement in compassionate experiences or behaviours. Furthermore, fears of compassion have been found to impede progress in psychotherapy. The 38-item fears of compassion scales (FCS) is a self-report questionnaire for measuring trait levels of fears of compassion (a) one receives from others (FCFO), (b) one feels towards others (FCTO) and (c) one feels for oneself (self-compassion; FSC). The FCS is an internationally used instrument of proven validity and reliability in both clinical and nonclinical samples. In the present study, a German translation of the FCS including its three subscales was provided, and the psychometric properties were examined in 430 participants from four different samples: (a) a sample from the general population; (b) a mixed sample of psychiatric residential and outpatients; (c) a clinical sample of residential and outpatients with a primary diagnosis of BPD and (d) a sample of healthy control participants. Internal consistencies were excellent for the German version of the FSC and acceptable to excellent for its subscales. Correlations with established measures of mental health demonstrate its validity. Additionally, the German FCS discriminates significantly between individuals from the general population and patients, thus supporting its specificity. The German FCS is suitable to detect potential obstacles in cultivating compassion in psychotherapeutic treatments and beyond.
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http://dx.doi.org/10.1002/cpp.2496DOI Listing
January 2021

Mechanical Characteristics of Ultrafast Zebrafish Larval Swimming Muscles.

Biophys J 2020 08 18;119(4):806-820. Epub 2020 Jul 18.

Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont. Electronic address:

Zebrafish (Danio rerio) swim within days of fertilization, powered by muscles of the axial myotomes. Forces generated by these muscles can be measured rapidly in whole, intact larval tails by adapting protocols developed for ex vivo muscle mechanics. But it is not known how well these measurements reflect the function of the underlying muscle fibers and sarcomeres. Here, we consider the anatomy of the 5-day-old, wild-type larval tail, and implement technical modifications to measuring muscle physiology in intact tails. Specifically, we quantify fundamental relationships between force, length, and shortening velocity, and capture the extreme contractile speeds required to swim with tail-beat frequencies of 80-100 Hz. Therefore, we analyze 1000 frames/s videos to track the movement of structures, visible in the transparent tail, which correlate with sarcomere length. We also characterize the passive viscoelastic properties of the preparation to isolate forces contributed by nonmuscle structures within the tail. Myotomal muscles generate more than 95% of their maximal isometric stress (76 ± 3 mN/mm) over the range of muscle lengths used in vivo. They have rapid twitch kinetics (full width at half-maximal stress: 11 ± 1 ms) and a high twitch/tetanus ratio (0.91 ± 0.05), indicating adaptations for fast excitation-contraction coupling. Although contractile stress is relatively low, myotomal muscles develop high net power (134 ± 20 W/kg at 80 Hz) in cyclical work loop experiments designed to simulate the in vivo dynamics of muscle fibers during swimming. When shortening at a constant speed of 7 ± 1 muscle lengths/s, muscles develop 86 ± 2% of isometric stress, whereas peak instantaneous power during 100 Hz work loops occurs at 18 ± 2 muscle lengths/s. These approaches can improve the usefulness of zebrafish as a model system for muscle research by providing a rapid and sensitive functional readout for experimental interventions.
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http://dx.doi.org/10.1016/j.bpj.2020.06.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451861PMC
August 2020

Investigation of the "central vein sign" in infratentorial multiple sclerosis lesions.

Mult Scler Relat Disord 2020 Oct 17;45:102409. Epub 2020 Jul 17.

Department of Neurology, Medical Faculty Mannheim and Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Theodor-Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany. Electronic address:

Background: Recently there has been an increasing interest in the "central vein sign" (CVS) in multiple sclerosis (MS) lesions. Infratentorial brain regions represent typical predilection sites for MS lesion development and are part of the current McDonald criteria to demonstrate dissemination in space, but only a few studies investigated the presence of the CVS in infratentorial MS lesions. The aim of this study was to investigate the CVS in infratentorial MS lesions.

Methods: 3T MRI data sets from 119 patients with relapsing MS were analysed. Chronic lesions were identified on T2-weighted images. Co-registered T2 / susceptibility-weighted images (SWI) were analysed for the presence of the CVS.

Results: A total of 527 lesions were analysed. A CVS was present in the majority of infratentorial lesions (62/88, 70%). There was no difference in the frequencies of the CVS of infratentorial lesions compared to paraventricular lesions (67/81, 83%; p = 0.06) or subcortical (150/209; 72%; p = 0.82) lesions. Infratentorial lesions showed a CVS more often than juxtacortical lesions (16/34; 47%; p = 0.02), while periventricular lesions showed a CVS more often than infratentorial lesions (97/115; 84%, p = 0.02).

Conclusion: CVS is a frequent finding in infratentorial MS lesions that may increase the diagnostic value in MS.
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http://dx.doi.org/10.1016/j.msard.2020.102409DOI Listing
October 2020

Rare Ectopic Pregnancies - A Literature Review for the Period 2007 - 2019 on Locations Outside the Uterus and Fallopian Tubes.

Geburtshilfe Frauenheilkd 2020 Jul 14;80(7):686-701. Epub 2020 Jul 14.

Charité - Universitätsmedizin Berlin, Klinik für Gynäkologie, Campus Virchow Klinikum, Berlin, Germany.

The majority of ectopic pregnancies (EP) are tubal pregnancies, but other implantation sites outside the uterus and tubes are also found. These rare EP locations present a particular diagnostic and therapeutic challenge. We present an overview of potential very rare locations of ectopic pregnancies, their symptoms, diagnosis and treatment, based on a systematic analysis of case reports. A literature review of the databases PubMed, Livivo and Google Scholar for the period 2007 to 2019 was carried out. A total of 113 publications were included in our review. These studies describe EP implantations in the posterior cul-de-sac, on the uterine serosa and uterine ligaments, in the vicinity of almost all intraperitoneal organs, on the abdominal wall as well as in retroperitoneal sites. The most common presenting symptom was abdominal pain occurring in different locations. The diagnostic procedures included various imaging procedures and/or explorative surgery at different advanced stages of pregnancy. The most common and preferred option was laparotomy for surgical treatment. The placenta was successfully resected in the majority of cases. A rare EP location should be considered when making a differential diagnosis in patients of child-bearing age with abdominal pain.
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http://dx.doi.org/10.1055/a-1181-8641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360401PMC
July 2020

Best Practices for Educating the Next Generation to Work With Older Adults.

Int J Aging Hum Dev 2020 12 8;91(4):359-361. Epub 2020 Jul 8.

5631 West Virginia University, Morgantown, WV, USA.

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http://dx.doi.org/10.1177/0091415020937587DOI Listing
December 2020

Wapl repression by Pax5 promotes V gene recombination by Igh loop extrusion.

Nature 2020 08 1;584(7819):142-147. Epub 2020 Jul 1.

Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.

Nuclear processes, such as V(D)J recombination, are orchestrated by the three-dimensional organization of chromosomes at multiple levels, including compartments and topologically associated domains (TADs) consisting of chromatin loops. TADs are formed by chromatin-loop extrusion, which depends on the loop-extrusion function of the ring-shaped cohesin complex. Conversely, the cohesin-release factor Wapl restricts loop extension. The generation of a diverse antibody repertoire, providing humoral immunity to pathogens, requires the participation of all V genes in V(D)J recombination, which depends on contraction of the 2.8-Mb-long immunoglobulin heavy chain (Igh) locus by Pax5. However, how Pax5 controls Igh contraction in pro-B cells remains unknown. Here we demonstrate that locus contraction is caused by loop extrusion across the entire Igh locus. Notably, the expression of Wapl is repressed by Pax5 specifically in pro-B and pre-B cells, facilitating extended loop extrusion by increasing the residence time of cohesin on chromatin. Pax5 mediates the transcriptional repression of Wapl through a single Pax5-binding site by recruiting the polycomb repressive complex 2 to induce bivalent chromatin at the Wapl promoter. Reduced Wapl expression causes global alterations in the chromosome architecture, indicating that the potential to recombine all V genes entails structural changes of the entire genome in pro-B cells.
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http://dx.doi.org/10.1038/s41586-020-2454-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116900PMC
August 2020

FYN and ABL Regulate the Interaction Networks of the DCBLD Receptor Family.

Mol Cell Proteomics 2020 10 30;19(10):1586-1601. Epub 2020 Jun 30.

Department of Biology, University of Vermont, Marsh Life Sciences, Burlington, Vermont, USA. Electronic address:

The Discoidin, CUB, and LCCL domain-containing protein (DCBLD) family consists of two type-I transmembrane scaffolding receptors, DCBLD1 and DCBLD2, which play important roles in development and cancer. The nonreceptor tyrosine kinases FYN and ABL are known to drive phosphorylation of tyrosine residues in YXXP motifs within the intracellular domains of DCBLD family members, which leads to the recruitment of the Src homology 2 (SH2) domain of the adaptors CT10 regulator of kinase (CRK) and CRK-like (CRKL). We previously characterized the FYN- and ABL-driven phosphorylation of DCBLD family YXXP motifs. However, we have identified additional FYN- and ABL-dependent phosphorylation sites on DCBLD1 and DCBLD2. This suggests that beyond CRK and CRKL, additional DCBLD interactors may be regulated by FYN and ABL activity. Here, we report a quantitative proteomics approach in which we map the FYN- and ABL-regulated interactomes of DCBLD family members. We found FYN and ABL regulated the binding of several signaling molecules to DCBLD1 and DCBLD2, including members of the 14-3-3 family of adaptors. Biochemical investigation of the DCBLD2/14-3-3 interaction revealed ABL-induced binding of 14-3-3 family members directly to DCBLD2.
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http://dx.doi.org/10.1074/mcp.RA120.002163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015000PMC
October 2020

Guideline-adherence in the treatment of symptomatic urolithiasis in children and adolescents in southwestern Germany.

BMC Urol 2020 Jun 26;20(1):76. Epub 2020 Jun 26.

Department of Urology and Paediatric Urology, Medical University Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.

Background: Approximately 1% of urolithiasis cases in Germany affect children. Interdisciplinary groups have agreed on national and international guidelines for children to recommend appropriate treatment pathways. The aim of this retrospective and preliminary study is to analyze whether adherence to current guidelines for pediatric stone disease in southwestern Germany is feasible.

Methods: During 2014 to 2017 24 children and adolescents (nine female, 15 male, median age 9.7 years), were treated for symptomatic urolithiasis in our institutions. We retrospectively collected clinical and operative courses. Clinical pathways were compared to previous guideline recommendations of the EAU 2014 and the German S2k guideline 2015.

Results: 17 of the 24 patients were treated according to guideline recommendations (71%). Non-adherency was based on parental decisions in two and technical/medical considerations in five cases. In 11 children (45.8%) secondary or adjunctive treatments were necessary, in three of the seven non-adherently treated (43%) and in eight of the 17 adherently treated children (47%).

Conclusion: Our daily treatment approach seems to comply well with current pediatric stone guidelines. Nevertheless, guideline-non-adherent decision making emphasizes their strength and limitations, as specific clinical situations in children may require an individual treatment plan, as non-predictable conditions may occur.
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http://dx.doi.org/10.1186/s12894-020-00643-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320579PMC
June 2020