RepoMed (Medizinische Hochschule Hannover)
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Genome-Wide Methylation Mapping Using Nanopore Sequencing Technology Identifies Novel Tumor Suppressor Genes in Hepatocellular Carcinoma.
No full textDownregulation of multiple tumor suppressor genes (TSGs) plays an important role in cancer formation. Recent evidence has accumulated that cancer progression involves genome-wide alteration of epigenetic modifications, which may cause downregulation of the tumor suppressor gene. Using hepatocellular carcinoma (HCC) as a system, we mapped 5-methylcytosine signal at a genome-wide scale using nanopore sequencing technology to identify novel TSGs. Integration of methylation data with gene transcription profile of regenerated liver and primary HCCs allowed us to identify 10 potential tumor suppressor gene candidates. Subsequent validation led us to focus on functionally characterizing one candidate-glucokinase (GCK). We show here that overexpression of GCK inhibits the proliferation of HCC cells via induction of intracellular lactate accumulation and subsequently causes energy crisis due to NAD+ depletion. This suggests GCK functions as a tumor suppressor gene and may be involved in HCC development. In conclusion, these data provide valuable clues for further investigations of the process of tumorigenesis in human cancer
High Incidence of Epileptiform Potentials During Continuous EEG Monitoring in Critically Ill COVID-19 Patients.
No full textObjective: To analyze continuous 1- or 2-channel electroencephalograms (EEGs) of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) with regard to occurrence of epileptiform potentials. Design: Single-center retrospective analysis. Setting: Intensive care unit of Hannover Medical School, Hannover, Germany. Patients: Critically ill COVID-19 patients who underwent continuous routine EEG monitoring (EEG monitor: Narcotrend-Compact M) during sedation. Measurements and Main Results: Data from 15 COVID-19 patients (11 men, four women; age: 19-75 years) were evaluated. Epileptiform potentials occurred in 10 of 15 patients (66.7%). Conclusions: The results of the evaluation regarding the occurrence of epileptiform potentials show that there is an unusually high percentage of cerebral involvement in patients with severe COVID-19. EEG monitoring can be used in COVID-19 patients to detect epileptiform potentials
Extracting data from graphs: A case-study on animal research with implications for meta-analyses.
Get PDFSystematic reviews with meta-analyses are powerful tools that can answer research questions based on data from published studies. Ideally, all relevant data is directly available in the text or tables, but often it is only presented in graphs. In those cases, the data can be extracted from graphs, but this potentially introduces errors. Here, we investigate to what extent the extracted outcome and error values differ from the original data and if these differences could affect the results of a meta-analysis. Six extractors extracted 36 outcome values and corresponding errors from 22 articles. Differences between extractors were compared using overall concordance correlation coefficients (OCCC), differences between the original and extracted data were compared using concordance correlation coefficients (CCC). To test the possible influence on meta-analyses, random-effects meta-analyses on mean difference comparing original and extracted data were performed. The OCCCs and CCCs were high for both outcome values and errors, CCCs were >0.99 for the outcome and >0.92 for errors. The meta-analyses showed that the overall effect on outcome was very small (median: 0.025, interquartile range: 0.016-0.046). Therefore, data extraction from graphs is a good method to harvest data if it is not provided in the text or tables, and the original authors cannot provide the data
Non-Invasive and Surgical Modalities for Scar Management: a Clinical Algorithm
No full textScars can lead to aesthetic and functional impairments. The treatment of scars requires meticulous planning and an individually adapted therapeutic strategy. A conceptual algorithm for scar treatment makes everyday clinical work easier for the practitioner and offers more safety for the patient. Based on a retrospective analysis of 1427 patients who presented for treatment of a variety of scars, we developed an algorithm for scar management and treatment. The treatments are presented using case descriptions. Additionally, an electronic search of MEDLINE, EMBASE, and ClinicalTrials.gov databases was performed utilizing combinations of relevant medical subject headings for "scar treatment", "hypertrophic scar treatment" and "keloid treatment". Reference lists of relevant articles and reviews were hand-searched for additional reports. Observed outcomes included: conservative scar therapy, minimally invasive scar therapy, and surgical scar therapy using local, regional and free flaps. With this work, we provide an algorithm for safe scar treatment. For better understanding, we have described a clinical case for each algorithm modality
Microbial influences on allergic inflammation: crosstalk of the C-type lectin receptors Dectin-1 and Dectin-2 and implications in allergy
No full textProcess control and in silico modeling strategies for enabling high density culture of human pluripotent stem cells in stirred tank bioreactors
No full textThe routine therapeutic and industrial applications of human pluripotent stem cells (hPSCs) require their constant mass supply by robust, efficient, and economically viable bioprocesses. Our protocol describes the fully controlled expansion of hPSCs in stirred tank bioreactors (STBRs) enabling cell densities of 35 3 106 cells/mL while reducing culture medium consumption by 75%. This is achieved by in silico process modeling and computable upscaling. We provide a detailed blueprint for systematic process development of hPSCs and their progenies
Einfluss des Alters auf die Überwachung der Narkosetiefe mit dem EEG-basierten Narcotrend Index während Sevoflurananästhesie bei Kindern unter 2 Jahren
No full textGC-MS Analysis of Biological Nitrate and Nitrite Using Pentafluorobenzyl Bromide in Aqueous Acetone: A Dual Role of Carbonate/Bicarbonate as an Enhancer and Inhibitor of Derivatization.
No full textCarbon dioxide (CO2) and carbonates, which are widely distributed in nature, are constituents of inorganic and organic matter and are essential in vegetable and animal organisms. CO2 is the principal greenhouse gas in the atmosphere. In human blood, CO2/HCO3- is an important buffering system. Inorganic nitrate (ONO2-) and nitrite (ONO-) are major metabolites and abundant reservoirs of nitric oxide (NO), an endogenous multifunctional signaling molecule. Carbonic anhydrase (CA) is involved in the reabsorption of nitrite and nitrate from the primary urine. The measurement of nitrate and nitrite in biological samples is of particular importance. The derivatization of nitrate and nitrite in biological samples alongside their 15N-labeled analogs, which serve as internal standards, is a prerequisite for their analysis by gas chromatography-mass spectrometry (GC-MS). A suitable derivatization reagent is pentafluorobenzyl bromide (PFB-Br). Nitrate and nitrite are converted in aqueous acetone to PFB-ONO2 and PFB-NO2, respectively. PFB-Br is also useful for the GC-MS analysis of carbonate/bicarbonate. This is of particular importance in conditions of pharmacological CA inhibition, for instance by acetazolamide, which is accompanied by elevated concomitant excretion of nitrate, nitrite and bicarbonate, as well as by urine alkalization. We performed a series of experiments with exogenous bicarbonate (NaHCO3) added to human urine samples (range, 0 to 100 mM), as well as with endogenous bicarbonate resulting from the inhibition of CA activity in healthy subjects before and after ingestion of pharmacological acetazolamide. Our results indicate that bicarbonate enhances the derivatization of nitrate with PFB-Br. In contrast, bicarbonate decreases the derivatization of nitrite with PFB-Br. Bicarbonate is not a catalyst, but it enhances PFB-ONO2 formation and inhibits PFB-NO2 formation in a concentration-dependent manner. The effects of bicarbonate are likely to result from its reaction with PFB-Br to generate PFB-OCOOH. Nitrate reacts with concomitantly produced PFB-OCOOH to form PFB-ONO2 in addition to the direct reaction of nitrate with PFB-Br. By contrast, nitrite does not react with PFB-OCOOH to form PFB-NO2. Sample acidification by small volumes of 20 wt.% aqueous acetic acid abolishes the effects of exogenous and endogenous bicarbonate on nitrite measurement
Klinische und radiologische Ergebnisse der Arthrolyse des arthrotischen oberen Sprunggelenks
No full textIs a Femoro-Acetabular Impingement Type Cam Predictable after Slipped Capital Femoral Epiphysis?
No full text(1) Background: Previous studies have proven a high incidence of a femoro-acetabular impingement (FAI) type cam in patients sustaining a slipped capital femoral epiphysis (SCFE). Thus, the current study analyzed, if a cam deformity is predictable after SCFE treatment; (2) Methods: 113 cases of SCFE were treated between 1 January 2005 and 31 December 2017. The radiological assessment included the slip angle after surgery (referenced to the femoral neck (epiphyseal tilt) and shaft axis as Southwick angle) and the last available lateral center edge angle (LCEA), the acetabular- and alpha angle. A correlation was performed between these parameters and the last alpha angle to predict a FAI type cam; (3) Results: After a mean follow-up of 4.3 years (±1.9; 2.0-11.2), 48.5% of the patients showed a FAI type cam and 43.2% a dysplasia on the affected side. The correlation between the epiphyseal tilt and alpha angle was statically significant (p = 0.017) with a medium effect size of 0.28; (4) Conclusions: The postoperative posterior epiphyseal tilt was predictive factor to determine the alpha angle. However, the cut-off value of the slip angle was 16.8° for a later occurrence of a FAI type cam indicating a small range of acceptable deviations from the anatomical position for SCFE reconstruction