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Bisacodyl and Sodium Picosulfate Improve Bowel Function and Quality of Life in Patients with Chronic Constipation—Analysis of Pooled Data from Two Randomized Controlled Trials

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Open Journal of Gastroenterology 2017年第1期7卷 32-43页

作者： Stefan müller-Lissner Erika Richter marion Eberlin Harald Weigmann tobias mück michael A. Kamm Department of Internal medicine Park-Klinik Weissensee Berlin Germany Sanofi-Aventis GmbH Frankfurt-Hoechst Germany St Vincent’s Hospital University of Melbourne Melbourne Australia

Background: Quality of life (QoL) is impaired in chronic constipation. Among nonprescription laxatives QoL data out of randomized controlled trials are available only for bisacodyl and sodium picosulfate (SPS). methods: In two randomized, double-blind, placebo-controlled, parallel-group trials, the efficacy and safety of treatment with either bisacodyl or SPS, respectively, were assessed. After a 2-week baseline period patients with functional constipation were randomized to a 4-week treatment with either bisacodyl (2 tablets = 10 mg), SPS (18 drops = 10 mg), or matching placebo in a ratio of active drug to placebo of 2:1. Dose reduction as well as resuming the original dose was permitted. Patients who did not experience a bowel movement for more than 72 h were allowed to use a bisacodyl suppository. The primary endpoint was the mean number of Complete Spontaneous Bowel movements (CSBms) per week during the trial. QoL was assessed using the Patient Assessment of Constipation (PAC)-QoL questionnaire. Results: Active treatment led to a greater improvement of PAC-QoL scores for every domain. Active treatment was also superior to placebo for all individual questions of the questionnaire. Of note, SPS or bisacodyl not only improved satisfaction with stool patterns (“quite a bit/extremely satisfied” in 12.8% of patients on placebo and 50.3% on active treatment) but bloating was also considerably ameliorated (“not at all feeling bloated” in 24.5% on placebo and 41.4% on active treatment). Conclusion: Bisacodyl and SPS not only improve stool variables but also quality of life in patients with chronic functional constipation. (EudraCT Nos. 2007-001991-34 and 2007-002087-10).

关键词： Constipation Laxative Bisacodyl Sodium Picosulfate Quality of Life

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modularization of adhesion G protein-coupled receptor(aGPCR)structure:how alternative splicing regulates synaptogenesis

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1793-1795页

作者： tobias Langenhan Rudolf Schönheimer Institute of Biochemistry Division of General BiochemistryMedical FacultyLeipzig UniversityLeipzigGermany Comprehensive Cancer Center Central Germany(CCCG) Leipzig UniversityLeipzigGermany Institute of Biology Faculty of Life SciencesLeipzig UniversityLeipzigGermany

A recent report has uncovered a fascinating aspect of how neurons utilize alternative splicing of transcripts of an adhesion G protein-coupled receptor(aGPCR)gene to serve specific functions in the life of a synapse.1 The work provides significant insight into the ability of cells to support distinct biochemical and physiological operations through post-transcriptional processing of genetic information that is encoded in a single aGPCR locus.

关键词： GPCR utilize operations

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Hyper spectral resolution stimulated Raman spectroscopy with amplified fs pulse bursts

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Light(Science & Applications) 2024年第3期13卷 566-576页

作者： Hongtao Hu tobias Flöry Vinzenz Stummer Audrius Pugzlys markus Zeiler Xinhua Xie Aleksei Zheltikov Andrius Baltuška Photonics Institute Technische Universität WienGußhausstraße 27-29Vienna A-1040Austria SwissFEL Paul Scherrer InstituteVilligen PSI 5232Switzerland Institute for Quantum Science and Engineering Department of Physics and AstronomyTexas A&M UniversityCollege StationTX 77843USA

We present a novel approach for Stimulated Raman Scattering(SRS)spectroscopy in which a hyper spectral resolution and high-speed spectral acquisition are achieved by employing amplified offset-phase controlled fs-pulse bursts.We investigate the method by solving the coupled non-linear Schrödinger equations and validate it by numerically characterizing SRS in molecular nitrogen as a model compound.The spectral resolution of the method is found to be determined by the inverse product of the number of pulses in the burst and the intraburst pulse separation.The SRS spectrum is obtained through a motion-free scanning of the offset phase that results in a sweep of the Raman-shift frequency.Due to high spectral resolution and fast motion-free scanning the technique is beneficial for a number SRS-based applications such as gas sensing and chemical analysis.

关键词： compound spectral resolution

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Impact of exercise on markers of B cell-related immunity:A systematic review

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Journal of Sport and Health Science 2024年第3期13卷 339-352,I0002页

作者： David Walzik Sergen Belen Karen Wilisch marie Kupjetz Silvana Kirschke tobias Esser Niklas Joisten Alexander Schenk Sebastian Proschinger Philipp Zimmer Division of Performance and Health(Sports medicine) Institute for Sport and Sport ScienceTU Dortmund UniversityDortmund 44227Germany

Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.methods:According to the Preferred Reporting Items for Systematic Reviews and meta-Analyses(PRISmA)guidelines,mEDLINE,Web of Science,and Embase were searched on march 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

关键词： Antibody B-lymphocyte Exercise Humoral immunity Immune system

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The Structure of Gravity Funnels and Stability Considerations of matter in SI Units

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第1期10卷 71-81页

作者： tobias Bartusch Bartusch Plasma and Vacuum Kissing Germany

This article describes an extension of the theory of vortices to electromagnetic types with a start point from known fluid systems. From this, properties of gravity-generating objects (particles and black holes) can be derived, which can also describe their possible interior. This also leads to questions about stability, which are then addressed and ultimately lead to considerations of black holes and their possible internal structure. The results fit into the observable areas and can also be directly verified because they were analytically calculated in SI units.

关键词： Black Hole Dark matter Electromagnetic Gravity Singularity Vortex

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Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell tobias Steinschaden Rose Horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA Department of Pathology and Laboratory medicine University of PennsylvaniaPhiladelphiaPAUSA medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

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Smart Approaches to Efficient Text mining for Categorizing Sexual Reproductive Health Short messages into Key Themes

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Open Journal of Applied Sciences 2024年第2期14卷 511-532页

作者： tobias makai mayumbo Nyirenda Department of Computer Science University of Zambia Lusaka Zambia

To promote behavioral change among adolescents in Zambia, the National HIV/AIDS/STI/TB Council, in collaboration with UNICEF, developed the Zambia U-Report platform. This platform provides young people with improved access to information on various Sexual Reproductive Health topics through Short messaging Service (SmS) messages. Over the years, the platform has accumulated millions of incoming and outgoing messages, which need to be categorized into key thematic areas for better tracking of sexual reproductive health knowledge gaps among young people. The current manual categorization process of these text messages is inefficient and time-consuming and this study aims to automate the process for improved analysis using text-mining techniques. Firstly, the study investigates the current text message categorization process and identifies a list of categories adopted by counselors over time which are then used to build and train a categorization model. Secondly, the study presents a proof of concept tool that automates the categorization of U-report messages into key thematic areas using the developed categorization model. Finally, it compares the performance and effectiveness of the developed proof of concept tool against the manual system. The study used a dataset comprising 206,625 text messages. The current process would take roughly 2.82 years to categorise this dataset whereas the trained SVm model would require only 6.4 minutes while achieving an accuracy of 70.4% demonstrating that the automated method is significantly faster, more scalable, and consistent when compared to the current manual categorization. These advantages make the SVm model a more efficient and effective tool for categorizing large unstructured text datasets. These results and the proof-of-concept tool developed demonstrate the potential for enhancing the efficiency and accuracy of message categorization on the Zambia U-report platform and other similar text messages-based platforms.

关键词： Knowledge Discovery in Text (KDT) Sexual Reproductive Health (SRH) Text Categorization Text Classification Text Extraction Text mining Feature Extraction Automated Classification Process Performance Stemming and Lemmatization Natural Language Processing (NLP)

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Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2349-2357页

作者： Rabea Voget Julian Breidenbach tobias Claff Alexandra Hingst Katharina Sylvester Christian Steinebach Lan Phuong Vu Renato H.Weiße Ulrike Bartz Norbert Sträter Christa E.müller michael Gütschow Pharmaceutical Institute Pharmaceutical&Medicinal ChemistryUniversity of BonnBonn 53121Germany Institute of Bioanalytical Chemistry Center for Biotechnology and BiomedicineLeipzig UniversityLeipzig 04103Germany Department of Natural Sciences University of Applied Sciences Bonn-Rhein-SiegRheinbach 53359Germany

A titrant for the SARS-CoV-2 main protease(m^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active m^(pro) by active-site titration.The covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant complex.Four fluorogenic substrates of m^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay conditions.By exploiting the new titrant,key kinetic parameters for the m^(pro)-catalyzed cleavage of these substrates were determined.

关键词： COVID-19 SARS-CoV-2 main protease Peptide nitriles Fluorogenic substrates Active-site titration X-ray crystallography Inner filter effect

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Organochlorides mediate Oxidation Reactions Induced by Low Dose Ionizing Radiation

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CCS Chemistry 2024年第7期6卷 1712-1720页

作者： Juncheng Liu tobias G.Brevé Bing Xu Peter-Leon Hagedoorn Antonia G.Denkova Rienk Eelkema Department of Radiation Science and Technology Delft University of Technology2629 JB Delft Department of Chemical Engineering Delft University of Technology2629 HZ Delft Department of Biotechnology Delft University of Technology2629 HZ Delft

The controlled release of drugs using local ionizing radiation presents a promising approach for targeted cancer treatment,particularly when applied in concurrent radio-chemotherapy.In these approaches,radiation-generated reactive species often play an important role.However,the reactive species that can be used to trigger release have low yield and lack selectivity.Here,we demonstrate the generation of highly oxidative species when aqueous solutions containing low concentrations of organochlorides(such as chloroform)are irradiated with ionizing radiation at therapeutically relevant doses.These reactive species were identified as peroxyl radicals,which formed in a reaction cascade between organochlorides and aqueous electrons.We employed stilbene-based probes to investigate the oxidation process,showing double bond oxidation and cleavage.To translate this reactivity into a radiation-sensitive material,we synthesized a micelle-forming amphiphilic block copolymer that has stilbene as the linker between two blocks.Upon exposure to ionizing radiation,the oxidation of stilbene led to the cleavage of the polymer,which induces the dissociation of the block-copolymer micelles and the release of loaded drugs.

关键词： drug delivery micelles radiation chemistry reactive oxygen species ionizing radiation reaction mechanisms

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No generality in biodiversity-productivity relationships along elevation in temperate and subtropical forest landscapes

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Forest Ecosystems 2024年第3期11卷 255-265页

作者： Jiayun Zou Yahuang Luo Rupert Seidl Dominik Thom Jie Liu Lisa Geres tobias Richter Linjiang Ye Wei Zheng Liangliang ma Jie Song Kun Xu Dezhu Li Lianming Gao Sebastian Seibold Ecosystem Dynamics and Forest management Research Group School of Life SciencesTechnical University of MunichHans-Carl-von-Carlowitz-Platz 285354FreisingGermany State Key Laboratory of Plant Diversity and Specialty Crops Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Germplasm Bank of Wild Species Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Lijiang Forest Biodiversity National Observation and Research Station Kunming Institute of BotanyChinese Academy of SciencesLijiang674100China Berchtesgaden National Park Doktorberg 683471Germany Gund Institute for Environment University of Vermont617 Main StreetBurlingtonVT 1105405USA Faculty of Biological Sciences Institute for EcologyEvolution and DiversityConservation BiologyGoethe University FrankfurtFrankfurt am MainGermany University of Chinese Academy of Sciences Beijing10049China TUD Dresden University of Technology Forest ZoologyPienner Str.701737TharandtGermany

An improved understanding of biodiversity-productivity relationships(BPRs)along environmental gradients is crucial for effective ecosystem management and biodiversity conservation.The stress-gradient hypothesis suggests that BPRs are stronger in stressful environments compared to more favorable conditions.However,there is limited knowledge regarding the variation of BPRs along elevational gradients and their generality across different landscapes.To study how BPRs change with elevation,we harnessed inventory data on 6,431 trees from152 plots surveyed twice in eight to ten year intervals in mountain forests of temperate Europe and subtropical Asia.We quantified the relationship between aboveground productivity and different biodiversity measures,including taxonomic,functional,and phylogenetic diversity.To elucidate the processes underlying BPRs,we studied the variation of different functional traits along elevation across landscapes.We found no general pattern of BPRs across landscapes and elevations.Relationships were neutral for all biodiversity measures in temperate forests,and negative for taxonomic and functional diversity in subtropical forests.BPRs were largely congruent between taxonomic,functional and phylogenetic diversity.We found only weak support for the stress-gradient hypothesis,with BPRs turning from negative to positive(effect not significant)close to the tree line in subtropical forests.In temperate forests,however,elevation patterns were strongly modulated by species identity effects as influenced by specific traits.The effect of traits such as community-weighted mean of maximum plant height and wood density on productivity was congruent across landscapes.Our study highlights the context-dependence of BPRs across elevation gradients and landscapes.Species traits are key modulating factors of BPRs and should be considered more explicitly in studies of the functional role of biodiversity.Furthermore,our findings highlight that potential trade-offs between conserving biodiversity and fostering ecos

关键词： Biodiversity-ecosystem functioning Climate mitigation Elevation gradients Forest management Forest productivity Functional traits Nature conservation Phylogenetic diversity

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