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Causes of obese sarcopenia - Investigation of the influence of obesity on skeletal muscle in a mouse model
No full textSarcopenia, an age related decline in muscle strength and function, is becoming increasingly relevant in an aging society. With rising obesity prevalence in recent years, this condition represents an important comorbidity, as both diseases are known to synergistically accelerate muscle strength decline. However, the underlying molecular pathogenesis needs further research. Our aim was to investigate the impact of obesity on skeletal muscle and provide a basis for future research on obese sarcopenia in an established obesity mouse model (loxTB Mc4r), where the skeletal muscle has not been studied yet. Histological and molecular analyses of lower limb muscles of one year old knock-out and wildtype mice were combined to evaluate muscle morphology, regeneration, atrophy, fiber composition, mitochondrial function, and inflammation. Histological analyses revealed fatty degeneration, macrophage invasion, and fiber type changes predominantly in proximal muscles of female knock-out mice. In parallel, qPCR analyses suggested compromised regeneration capacity and implicated iNOS as a potential mediator of an adipo-myogenic effect. In conclusion, obesity induces sex-dependent myopathic changes that overlap with sarcopenia-related alterations, highlighting the importance of studying both synergistic and sex-specific effects of these conditions.2026-09-3
Nephroprotective effect of a semaphorin3a antibody in a mouse model of Alport syndrome
No full textBeim Alport Syndrom, einer hereditären Erkrankung, kommt es aufgrund von Veränderungen im Kollagen IV, welches sich in der glomerulären Basalmembran in den Nieren befindet, zu inflammatorischen und profibrotischen Prozessen lokal. Durch diese Veränderungen und Prozesse wird die Schlitzmembran, welche durch die Podozyten gebildet wird, in ihrer Stabilität negativ beeinflusst und die renale Funktion nimmt ab. Bei Nierenschädigung ist das Protein Semaphorin3a erhöht und über Nephrin destabilisiert es das Aktinzytoskelett des Podozyten und damit die Schlitzmembran. Als möglicher neuer Therapieansatz wurde in diesem Vorhaben ein Semaphorin3a-Antikörper untersucht am etablierten COL4A3 Mausmodell. Durch den Antikörper soll das Aktinzytoskelett stabilisiert werden und damit ein Verstreichen der Fußfortsätze des Podozyten und ein Voranschreiten einer Nierenerkrankung vermindert werden. Das Medikament wurde ab Tag 42 den Mäusen verabreicht und verblindet mit einem Placebo verglichen. In der Überlebenszeit der Mäuse zeigte sich kein Unterschied. Weitere Untersuchungen wurden in Präparationsgruppen durchgeführt. In der immunhistochemischen Färbung mit Laminin und Fibronektin zeigte sich zeigte sich die Tendenz einer verminderten tubulointerstitiellen Fibrosierung. Es war zunächst eine Verbesserung in der Albuminurie zu erkennen, welche mittels Proteinelektrophorese untersucht worden war. Dieser Unterschied war im Verlauf der weiteren Wochen nicht mehr nachweisbar und auch in den Serumwerten von Harnstoff- und Cholesterin zeigte sich kein Unterschied in den beiden Gruppen.Alport syndrome, a hereditary disease, causes local inflammatory and profibrotic processes due to changes in collagen IV, which is found in the glomerular basement membrane in the kidneys. These changes and profibrotic processes negatively affect the stability of the slit membrane formed by the podocytes, leading to a decline in renal function. In kidney damage, the protein semaphorin 3a is elevated and, via nephrin, destabilizes the actin cytoskeleton of the podocyte and thus the slit membrane. As a possible new therapeutic approach, a semaphorin 3a antibody was investigated in this project using the established COL4A3 mouse model. The antibody is intended to stabilize the actin cytoskeleton, thereby reducing the loss of podocyte foot processes and the progression of kidney disease. The drug was administered to the mice from day 42 and compared with a placebo in a blinded trial. No difference was observed in the survival time of the mice. Further investigations were carried out in preparation groups. Immunohistochemical staining with laminin and fibronectin showed a tendency toward reduced tubulointerstitial fibrosis. Initially, an improvement in albuminuria was observed, which had been examined using protein electrophoresis. This difference was no longer detectable in the course of the following weeks, and there was also no difference in the serum values of urea and cholesterol in the two groups.2026-10-1
Self-assembly-induced optical properties of carbohydrate derivatives
No full textStructural color is a fascinating form of coloration generating from the interaction between incident light and periodic structures at a length scale comparable to the optical wavelength. Unlike the mechanism of structural color formation, fluorescent color is produced by the emission of light from electronically excited states of certain chemicals after they absorb light. Both structural and fluorescent color of materials hold great promise for a wide range of applications, including imaging, sensing, coding, anti-counterfeiting, and encryption.
In this thesis, I first prepared the solution-derived spherulites with unique interconnected structural and fluorescent colors, self-assembled from stearoylated monosaccharides at room temperature. D-galactose stearoyl esters self-assemble into banded spherulites, containing twisted nanoplates and interconnected simultaneously changing structural and fluorescent colors. In comparison, D-mannose stearoyl esters can only form non-banded spherulites, which contain oriented nanoplates and uniform structural and fluorescent colors. Such materials revealed a novel negative correlation between fluorescence and birefringence, termed as alignment-promoted quenching propensity. Remarkably, the solid-state fluorescence quantum yields (FLQYs) of galactose and mannose-derived spherulites are as high as 49 ± 2% and 51 ± 2% respectively, approximately ten times higher than those of unmodified monosaccharides. These quantum yield values are even comparable to those of conventional aromatic chromophores. Moreover, these spherulites manifested an unexpected excitation-dependent multicolor photoluminescence with a broad-spectrum emission (410−620 nm). They show multiple peaks in the photoluminescent emission spectra and broad fluorescence lifetime distributions, which should be attributed to the clustering of a variety of oxygen-containing functional groups as the emissive moieties.
Then, inspired by the intriguing optical properties of the monosaccharide-based spherulites, surface-stearoylated/lauroylated cellulose nanocrystals (CNCs) and polymeric cellulose stearoyl/lauroyl esters were prepared and allowed to construct macroscale helices (MHs) and porous bowl-shaped microparticles (BSMPs). Surprisingly, the two superstructures are highly emissive, with unanticipated high solid-state fluorescence quantum yields (FLQYs) of 86% and 91%, which are the highest among reported biomass-based systems. Specifically, surface-stearoylated CNCs and cellulose stearoyl esters co-assemble into MHs (FLQY: 86%) with diameters of 32−104 μm, consisting of layered nanoplates with thicknesses of 44−94 nm. Meanwhile, surface-lauroylated CNCs and cellulose lauroyl esters co-assemble into porous BSMPs (FLQY: 91%) with diameters of 8−19 μm, consisting of nanosized flaky structures with thicknesses of 70−120 nm. The two superstructures show excitation-dependent fluorescence in a broad wavelength range. The outstanding FLQYs are ascribed to the synergism of the dense oxygen clusters and abundant van der Waals interactions and hydrogen bonds between side stearoyl or lauroyl groups, which can promote through-space electron delocalization, ultimately improving fluorescence performance. These results were rationalized by theoretical calculations. Such superstructures exhibited great potential for stable anti-counterfeiting materials due to the excellent regeneration ability as well as structural stability of the oxygen clusters.
In addition to the stearoylated and lauroylated carbohydrates mentioned above, D-glucose 11-octadecylthioundecanoate (D-Glc-C11S18E) was prepared as well. D-Glc-C11S18E can self-assemble into microspheres with diameters of 3−6 μm, composed of nanospheres with diameters of 100−300 nm. Within these nanospheres, a lamellar structure formed by octadecylthioundecanoyl groups (C29 lamella) developed in the interior, while a lamella formed by octadecyl groups (C18 lamella) appeared at the interfaces between adjacent nanospheres. Upon heating to 50 °C, the C18 lamella dissociated into an irregular structure, whereas the C29 lamella remained intact. When cooled to 20 °C, the C18 lamella reformed, demonstrating a selectively reversible self-assembly behavior for the two lamellar structures. When dispersed in methanol, the clustered microspheres dissociated into individual nanospheres at 50 °C, and individual ones reassembled into clustered ones at 20 °C, showing a reversible morphological nanostructure organization. This reversible structural transition was accompanied by fluorescence modulation, as the C18 and C29 lamellae induced distinct oxygen cluster environments. Notably, both the nanostructural and fluorescent modulations were reversible over at least ten heating−cooling cycles without fatigue. Benefiting from the reversible fluorescence, a fluorescent logic gate was constructed. In addition to providing fresh ideas for fundamental self-assembly study, these findings offer inspirations for developing smart optoelectronic devices based on reversible self-assembly.
This thesis is a cumulative work including 3 publications. Two were already published and one was submitted to peer-reviewed journals. The background, objective of the study, results and discussion, and general conclusion and perspectives are presented in Section 1-4.2026-03-0
The role of STAT1 signal transduction in the pathogenesis of Alzheimer’s disease
No full textChronic neuroinflammation is considered a key hallmark of Alzheimer’s disease (AD) and may represent a central mechanism in its pathogenesis. Microglia, the resident immune cells of the central nervous system (CNS), are crucial mediators in this complex and dysregulated process. Under physiological conditions, microglia contribute to neural homeostasis through functions such as synaptic pruning and surveillance. In response to CNS injury or infection, they constitute the first line of immune defense by initiating inflammatory responses, producing reactive oxygen species (ROS), and performing phagocytosis of pathogens and cellular debris. However, when chronically dysregulated - as observed in AD - microglial activity can exert significant harm on the neuronal environment, primarily through continuously activated cytotoxic mechanisms. To selectively alter microglial activation pathways and thereby investigate the impact of microglial modulation rather than complete deletion or suppression, we generated AD mouse models with impaired interferon-α and-γ (IFN) signaling. This was achieved by selectively disrupting STAT1 signal transduction. Specifically, we crossed the established 5xFAD transgenic model with either STAT1-/- mice, which are devoid of both IFN-α and-γ signaling, or STAT1-F77Aki/ki mice, which exhibit dysfunctional STAT1 signaling and consequently lack IFN-γ signaling alone. As a third model, we generated the Tg4-42/STAT1-/- line by crossing the Tg4-42 AD model, characterized by intraneuronal Aβ4-42 accumulation and CA1 region specific neuronal loss in the absence of extracellular plaques, with the STAT1-/- line. We questioned whether selective inhibition of IFN signaling would impact the progression of AD pathologies including amyloid-β accumulation, neuroinflammation and cognitive deficits. Additionally, we sought to explore how specific microglial functions - such as phagocytosis, plaque compaction, and cytotoxic actions towards surrounding neuronal tissue - would be affected by the absence of functional IFN signaling in the context of amyloid pathology. Counterintuitively, microglial activation was not suppressed or even reduced, but rather elevated, particularly in response to the combined deficiency in IFN-α and IFN-γ sig naling in the newly generated 5xFAD/STAT1-/- mouse line. Employing bulk transcriptome analysis, RT-qPCR, and immunohistochemical techniques, we demonstrated that 5xFAD/STAT1-/- mice displayed an earlier and more pronounced microglial response. This was characterized by increased expression of disease-associated microglia (DAM) signature genes, increased plaque coverage, and elevated Aβ peptide internalization. While the overall plaque burden, as assessed by 3D light-sheet microscopy, was significantly reduced, total Aβ concentration levels in the SDS-soluble fraction, measured by electrochemiluminescence assays, remained unchanged. We further demonstrated at the immunohistochemical level that this overt discrepancy was likely due to enhanced microglia-mediated plaque compaction in the 5xFAD/STAT1-/- mice. The significantly increased plaque compaction was accompanied by reduced axonal dystrophy around the dense-core plaques. Consistent with the reduced axonal damage, we also observed a complete rescue of spatial memory deficits, assessed by the novel object location paradigm. Although the effects on microglia were less pronounced and partially different in the 5xFAD/STAT1-F77Aki/ki line, a similar neuropathological pattern was observed, with reduced extracellular plaque burden despite unchanged Aβ concentration levels. This was again accompanied by increased plaque compaction, reduced axonal dystrophy and a restoration of spatial memory function. Our findings underscore the central and crucial role of microglia in the progression of AD-related pathologies. By appropriately performing functions such as scavenging and internalizing Aβ peptides, followed by remodeling and compaction of extracellular plaques, microglia might play a decisive role in mediating whether amyloid accumulation translates into neurotoxic effects and progresses towards exacerbated neuropathology. We therefore identify their delicately regulated activation, which enables them to adopt a range of functions and dynamically interchangeable phenotypic states, as a potentially critical regulatory node for therapeutic intervention and a deeper un derstanding of the disease mechanisms in AD.2026-06-2
- an MRI study-
No full textBackground: Early atrial alterations in asymptomatic systolic heart failure (NYHA I) remain insufficiently defined. We aimed to quantify left- (LA) and right-atrial (RA) function using cardiovascular magnetic resonance (CMR) feature tracking (FT) and volumetry, and to assess associations with exercise capacity.
Methods: In this cross-sectional substudy, 20 NYHA I patients (LVEF ≤ 40%, high exercise performance) from the TransitionCHF cohort were compared with 20 healthy controls. Phasic atrial strain parameters (εs/reservoir, εe/conduit, εa/booster) and strain rates (SRs, SRe, SRa) were derived for LA/RA, along with volumes (Vmax, Vpac, Vmin) and atrial ejection fractions; linear regression with peak VO₂/kg was performed.
Results: LA εs and εe were reduced in patients (εs 30.8 ± 10.4 % vs. 44.3 ± 18.2 %, p = 0.007; εe 14.6 ± 6.9 % vs. 26.6 ± 13.1 %, p = 0.001), whereas εa was preserved (p = 0.618). LA minimal volume was higher (41.5 ± 23.4 ml vs. 26.9 ± 11.2 ml; p = 0.006), and total/booster LA ejection fractions were lower. RA strain values did not differ significantly, but RA strain rates were lower (SRs p = 0.003; SRe p = 0.003; SRa p = 0.030); RA ejection fractions showed no significant group differences. As expected, LVEF was reduced in patients (44.0 ± 5.9 % vs. 68.0 ± 6.1 %; p < 0.001). In patients, LA εe correlated with peak VO₂/kg (R² = 0.414; p = 0.004).
Conclusions: Even at the asymptomatic NYHA I stage, LA reservoir and conduit functions are impaired while booster function is preserved, alongside increased LA minimal volume indicating early dilatation. The correlation between LA Conduit Strain and exercise capacity supports functional relevance and highlights atrial FT metrics as potential early markers. Confirmation in larger, prospective cohorts is warranted.2026-11-2
Synthesis and characterization of fluorescent probes targeting Histone Deacetylase 6 for live cell imaging
No full textHistone Deacetylase 6 (HDAC6) is a unique enzyme that plays a central role in major cellular processes, including cytoskeletal regulation, protein quality control, and stress responses. Its dysregulation is linked to many diseases, from cancer to neurodegeneration, making it a critical therapeutic target. However, studying the dynamic functions of HDAC6 in its native cellular environment has been hampered by a lack of specific chemical tools. The development of selective, live-cell compatible fluorescent probes is essential for visualizing HDAC6 and elucidating its complex biological roles in real-time. This thesis reports the rational design, synthesis, and characterization of a novel, high-performance fluorescent probe for imaging HDAC6 in living cells. Employing a modular design strategy, a library of probes was synthesized based on established HDAC6 inhibitor. A robust, cell-based screening platform was developed, utilizing a panel of U-2 OS cell lines engineered to express individual Halo-tagged HDACs (HDAC1-8). This platform enabled the quantitative evaluation of probe selectivity via co-localization analysis. Through this high-throughput screening, the Nexturastat A scaffold was identified as a superior recognition motif, exhibiting exceptional selectivity for HDAC6. A subsequent, rigorous structure-activity relationship (SAR) study was performed to optimize the probe's performance. This systematic optimization led to the development of 6SiR-C3-NextA, which incorporates a bright, photostable, and far-red silicon-rhodamine (SiR) fluorophore, a C3 alkyl linker, and a hydroxamic acid zinc-binding group. Comprehensive characterization demonstrated that 6SiR-C3-NextA binds to HDAC6 with high affinity (Kd = 24 nM) and excellent selectivity. Crucially, the probe was found to be highly suitable for live-cell imaging, exhibiting minimal cytotoxicity and no significant perturbation of the cell cycle at effective imaging concentrations. The probe successfully visualized endogenous HDAC6 in a diverse panel of cell lines. Its on-target specificity was validated through competitive inhibition assays and co-localization with a specific anti-HDAC6 antibody. The utility of 6SiR-C3-NextA was further demonstrated in biological investigations, facilitating high-resolution imaging of HDAC6's association with the microtubule network and its dynamic recruitment to stress granules following osmotic shock. While the probe performed exceptionally well in most cell types, its application in primary neurons suggested some off-target interactions, highlighting an area for future refinement.2026-11-0
Strahlenbelastung der Schilddrüse bei der ureterorenoskopischen Steinentfernung und der Effekt von Sternum- Schilddrüsen- Strahlenschutzkragen
No full textBei der Schilddrüse handelt es sich um ein strahlensensibles Organ. Organdysfunktionen wie Hypo-, seltener Hyperthyreosen werden nach Strahlenbelastung beobachtet, ebenso wie die Ausbildung von Adenomknoten oder die Induktion von Schilddrüsenkarzinomen. Wir untersuchten die Strahlenbelastung der Schilddrüse bei der ureterorenoskopischen Steinentfernung, dem häufigsten unter Röntgenkontrolle durchgeführten Eingriff in der Urologie.
Die Strahlenbelastung der Schilddrüse wurde in einem Alderson-Phantommodell sowie unter real-life-Bedingungen bei drei Operateuren gemessen und mit dem im Röntgengerät gemessenen Dosis-Flächen-Produkt korreliert. Die gemessenen Werte wurden retrospektiv anhand der im Röntgengerät für alle ureterorenoskopischen Steinentfernungen eines Jahres dokumentierten Dosis-Flächen-Produkt auf eine jährliche Strahlenbelastung sowie auf die Strahlenbelastung im Laufe eines Berufslebens hochgerechnet. Die Strahlenbelastung wurde als absolut an den Dosimetern gemessene Strahlenbelastung, als relative Strahlenbelastung nach Abzug der Hintergrundstrahlung und zusätzlich unter Korrektur auf die unteren Messgrenzen der Dosimeter sowohl vor wie auch hinter einem Sternum-Schilddrüsen-Strahlenschutzkragen dokumentiert. Zusätzlich erfolgte die Messung der Augenlinsendosis als möglichem Surrogatparameter zur Messung der Schilddrüsendosis.
Unsere Ergebnisse zeigen im Alderson-Phantommodell, dass bei Verwendung von Sternum-Schilddrüsen-Strahlenschutzkragen auch bei ansteigender Strahlenbelastung durch längere Durchleuchtungszeiten (maximal 0,054 mSv vor dem Sternum-Schilddrüsen-Strahlenschutzkragen bei 180 Sekunden Durchleuchtungszeit) die Strahlenbelastung hinter dem Sternum-Schilddrüsen-Strahlenschutzkragen unter die untere Messgrenze der Dosimeter von 0,014 mSv gesenkt werden kann;
Unter real-life-Bedingungen wurde die Strahlenbelastung bei den von den drei Operateuren durchgeführten 90 Ureterorenoskopie von 0,770 mSv auf 0,167 mSv (absolut gemessene Strahlendosis), bzw. von 0,701 mSv auf 0,098 mSv (relative Strahlenbelastung nach Abzug der Hintergrundstrahlung) bzw. von 0,701 mSv auf 0,178 mSv (Strahlenbelastung unter Berücksichtigung der unteren Dosimeter-Grenzwerte) gesenkt. Dies entspricht einer Strahlendosisreduktion von 78,3%, 86,0 % nach Abzug der Hintergrundstrahlung bzw. mindestens von 74,6% unter Berücksichtigung der unteren Dosismeter-Messgrenzen.
Diese würde unter real-life-Bedingungen bei Verwendung eines Sternum-Schilddrüse-Strahlenschutzkragen eine Reduktion der Strahlenbelastung bei den einzelnen Operateuren (abhängig von der Zahl der durchgeführten Eingriffe) um mindestens 0,245 bis 0,534 mSv pro Jahr, entsprechend um 70,0 % bis 83,4 % bedeuten. Hochgerechnet auf ein Berufsleben ergäbe sich damit eine Reduktion der Strahlenbelastung von 10,5 mSv bis 21,9 mSv auf 2,5 mSv bis 5,9 mSv.
Dabei lässt sich die nicht routinemäßig mitgemessene Strahlenbelastung an der Schilddrüse gut durch eine simultan gemessene Augenlinsendosis abschätzen, die mittels kommerziell erhältlichen Augenlinsendosimeter bestimmt werden kann. Der Korrelationskoeffizient betrug in unseren Untersuchungen zwischen der am vor dem Sternum-Schilddrüsen-Strahlenschutzkragen befestigten Dosimeter gemessenen Strahlendosis und der Augenlinsendosis 0,869.
Insgesamt war aber nach unserer Untersuchung die Strahlenbelastung der Schilddrüse bei Verwendung moderner digitaler Röntgenarbeitsplätze sehr gering. Im Vergleich dazu lag der Dosisgrenzwert für die jährliche Strahlenbelastung der Schilddrüse in der früheren Röntgenverordnung bei 300 mSv. Im aktuellen Strahlenschutzgesetz bzw. der aktuellen Strahlenschutzverordnung wird ein Grenzwert für die jährliche Strahlenbelastung der Schilddrüse ist nicht mehr definiert.
Die Strahlenbelastung der Schilddrüse konnte in unseren Untersuchungen durch die Verwendung von Sternum-Schilddrüsen Strahlenschutzkragen auf die Größenordnung der natürlichen Hintergrundstrahlung bzw. der unteren Messgrenzen der verwendeten Dosimeter gesenkt werden. Ohne Verwendung eines Sternum-Schilddrüsen-Strahlenschutzkragens beträgt die Strahlenbelastung für den einzelnen operativen Eingriff ca. 0,009 mSv, Werte die auch in anderen Situationen wie z.B. Interkontinentalflügen erreicht werden. Die in unseren Untersuchungen kalkuliert zusätzliche Strahlenbelastung der Schilddrüse im Verlauf eines Berufslebens ohne Verwendung eines Sternum-Schilddrüsen-Strahlenschutzkragen liegen dabei weit unterhalb der Werte, bei denen ein deterministischer Strahlenschaden eintritt. Unter der Annahme von linear-non-threshold Strahleneffekte könnten im Laufe eines Berufslebens zusätzlich bei 0,2 bis 2,2 von 100.000 Männern bzw. 0,8 bis 20,7 pro 100.000 Frauen ein zusätzliches Schilddrüsenkarzinom induziert werden. Ein Restrisiko für stochastische Strahlenschäden kann letztendlich wie immer nicht ausgeschlossen.
Ob allerdings diese geringe Strahlenbelastung der Schilddrüse bei der ureterorenoskopischen Steinentfernung das Tragen von Sternum-Schilddrüsen-Strahlenschutzkragen zwingend erforderlich macht, z.B. durch Regelungen in Dienstanweisungen, muss aufgrund unserer Untersuchungen kritisch hinterfragt werden.The thyroid gland is a radiation-sensitive organ. Organ dysfunctions such as Hypothyroidism, more rarely
hyperthyroidism, is observed after radiation exposure, as are the Formation of adenoma nodules or the induction
of thyroid carcinomas. We investigated the radiation exposure of the thyroid gland during ureterorenoscopic
Stone removal, the most common procedure performed under X-ray control in the Urology.
The radiation exposure of the thyroid gland was calculated in an Alderson phantom model as well as under real-
life conditions with three surgeons and with the X-ray machine measured dose-area product. The measured values
were retrospectively on the basis of the X-ray machine for all ureterorenoscopic stone removals in a year
documented dose-area product to an annual radiation exposure as well as to the radiation exposure in the course
of a working life. The radiation exposure was as absolute radiation exposure measured at the dosimeters, as
relative radiation exposure after deduction of the background radiation and additionally with correction to the
lower Measurement limits of the dosimeters both in front of and behind a sternum thyroid radiation protection
collar documented. In addition, the eye lens dose was measured as a possible surrogate parameter for measuring
thyroid dose.
Our results show in the Alderson phantom model that when sternum thyroid radiation protection collar can also
be used in the event of increasing radiation exposure due to prolonged fluoroscopy times (maximum 0.054 mSv
before the sternum thyroid radiation protection collar at 180 seconds fluoroscopy time) the sternum thyroid
radiation protection collar below the lower measurement limit of the dosimeter of 0.014 mSv;
Under real-life conditions, the radiation exposure of the patients led by the three surgeons from 0.770 mSv to
0.167 mSv (absolute measured radiation dose), or from 0.701 mSv to 0.098 mSv (relative radiation exposure after
deduction background radiation) or from 0.701 mSv to 0.178 mSv (radiation exposure below consideration of the
lower dosimeter limits). This corresponds to a Radiation dose reduction of 78.3%, 86.0% after deduction of
background radiation or of at least 74.6% taking into account the lower dose meter measurement limits.
This would be used under real-life conditions when using a sternum thyroid Radiation protection collar reduces
radiation exposure for individual surgeons (depending on the number of procedures performed) by at least 0.245
to 0.534 mSv per year, corresponding to 70.0 % to 83.4 %. Extrapolated to a working lifetime this would result in a
reduction of the radiation exposure from 10.5 mSv to 21.9 mSv to 2.5 mSv to 5.9 mSv.
The radiation exposure to the thyroid gland, which is not routinely measured, can be by means of a
simultaneously measured ophthalmic lens dose, which is measured by means of commercially available eye lens
dosimeter. The correlation coefficient in our investigations between the pre-star thyroid radiation protection collar
and the radiation dose measured by the radiation protection collar and the Eye lens dose 0.869.
Overall, however, according to our examination, the radiation exposure of the thyroid gland was Use of modern
digital X-ray workstations very low. In comparison, the Dose limit for the annual radiation exposure of the thyroid
gland in the former X-ray prescription at 300 mSv. In the current Radiation Protection Act or the current Radiation
Protection Ordinance sets a limit value for the annual radiation exposure of the Thyroid gland is no longer
defined.
In our investigations, the radiation exposure of the thyroid gland could be determined by the Use of sternum
thyroid radiation protection collar on the order of magnitude of the natural background radiation or the lower
measurement limits of the used dosimeter. Without the use of a sternum thyroid radiation protection collar, the
radiation exposure for the individual surgical procedure is approx. 0.009 mSv, values that are also achieved in
other situations such as intercontinental flights . The additional radiation exposure of the thyroid gland in the
course of a working life without the use of a sternum thyroid radiation protection collars are far below the values
at which a deterministic radiation damage occurs. Assuming linear-non-threshold radiation effects, in the course
of a working life in additionally at 0.2 to 2.2 per 100,000 men or 0.8 to 20.7 an additional thyroid carcinoma can be
induced for every 100,000 women. A residual risk for stochastic radiation damage can ultimately not be ruled out,
as always.
However, whether this low radiation exposure of the thyroid gland can be observed in the ureterorenoscopic
Stone removal the wearing of sternum thyroid radiation protection collar mandatory e.g. through regulations in
service instructions, must be critically questioned.2026-03-0
Potassium Channel Simulation with Force Field Development and Enhanced Sampling
No full textPotassium (K+) channels are a type of membrane protein that selectively permeates K+ ions. They play important roles in several biological processes, including regulating membrane potential, neuronal excitability, and muscle contraction. The study of K+ channel has can help us understand the K+ channel related neuronal or cardiac action1, some cancer2, and autoimmune diseas3. Molecular dynamics simulation provides atomistic spatial resolution and ps to μs time resolution to the function and dynamics of K+ channel.
To better simulate K+ channels, I have developed sets of force field parameters for more accurate description and enhanced sampling technic for faster sampling. In the force field project, I introduced polarization to fix charge force field in a mean field treatment. By scaling down the charge, which is mathematically the same as adding relative permittivity to the medium between MD particles, experimental conductance, current-voltage response, and K+/Na+ selectivity can be qualitatively reproduced. In the enhanced sampling project, I developed a simulation package that can perform grand canonical insertion/deletion and Hamiltonian replica exchange at the same time. With the ability to enhance water sampling, this package has been tested in K+ channel water sampling and relative binding free energy, and the package has demonstrated robustness and usefulness in both test cases.2026-09-0
Potential effects of different treatment in multiple sclerosis on CD20 positive T cells
No full textMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by inflammatory lesions in brain tissue. This study examined disease-modifying therapies (DMTs) with immunomodulatory potential, such as dimethyl fumarate (DMF), fingolimod (FTY), natalizumab (NAT), glatiramer acetate (GA), and anti-CD20 antibodies, including rituximab (RTX) and ocrelizumab (OCR). Previous research has identified a population of T cells that express the B cell antigen CD20 on their surface. These cells are thought to play a role in MS pathogenesis. This study focused on this CD20+ T cell population, demonstrating its increased presence and proinflammatory phenotype in MS patients. Blood samples from MS patients were stained with fluorescent extracellular and cytokine markers. The immune cells, particularly the CD20+ T cells, were classified before and during treatment with one of the DMTs using flow cytometry (FACS) analysis. The stage of maturation and immunological properties were examined in particular. The results showed that anti-CD20 antibodies most effectively reduced the number of CD20+ T cells in the peripheral blood but did not affect the pathogenic properties of CD20+T cells. DMF was significantly more effective in altering phenotype and function of CD20+ T cells because it reduced their inflammatory properties. FTY prevented immune cells from being flushed out of the lymph nodes. This was accompanied with a reduction in T cells in the peripheral blood, including a reduction in CD20+ T cells. Regarding the phenotype of the CD20+ T cells in the peripheral blood, a reduction in proinflammatory properties was observed; however, it was less pronounced than with DMF. Interestingly, this study showed a tendency for NAT to activate CD20+ T cells and enhance their proinflammatory properties. Due to small sample size, the results of the samples treated with GA must be interpreted with caution. However, the study showed that GA therapy significantly reduced the activation of CD20+ T cells, highlighting the immunomodulatory properties of GA. In summary, the study demonstrated that CD20+ T cells play a pivotal role MS pathogenesis and that established MS therapies affect the function and phenotype of this proinflammatory cell population differently.2026-03-1
Quality of Patient-Centered eHealth Information on Erosive Tooth Wear: Systematic Search and Evaluation of Websites and YouTube Videos
No full textBedingt durch den voranschreitenden Digitalisierungsprozess nimmt die Anzahl an Internetnutzenden, die Gesundheitsinformationen im Internet suchen, immer weiter zu. Aufgrund des Kariesrückgangs rücken erosive Zahnhartsubstanzdefekte vermehrt in den Fokus. Inwieweit sich Patient*innen zuverlässig über erosive Zahnhartsubstanzdefekte im Internet informieren können ist aktuell jedoch unklar.
Im Rahmen der Studie wurden deutschsprachige Inhalte (Websites und YouTube-Videos) verschiedener Anbieter anhand einer systematischen Suchstrategie identifiziert. Von den Anbietern wurden demografische Daten und praxisspezifische Parameter extrahiert sowie der Informationsumfang der Inhalte im Hinblick auf erosive Zahnhartsubstanzdefekte bewertet. Zudem wurde die Qualität der Websites anhand verschiedener Domänen untersucht: Technische und funktionelle Aspekte (LIDA), Lesbarkeit (FLESCH), allgemeine Qualität und Zuverlässigkeit als Informationsquelle (DISCERN). Der statistische Vergleich zwischen den verschiedenen Domänen, den verschiedenen Anbietern und den verschiedenen Inhalten erfolgte mittels Friedman-Test, Kruskal-Wallis-Tests und Wilcoxon-Test. Der potentielle Einfluss praxisspezifischer Parameter wurde mittels generalisierter linearer Modelle untersucht.
In die Studie wurden 231 Websites und sieben YouTube-Videos eingeschlossen. Die Mehrheit der eingeschlossenen Websites werden von privaten Zahnarztpraxen, gefolgt von privaten Praxisgesellschaften und Fachgesellschaften, bereitgestellt. Während technische und funktionelle Aspekte am höchsten bewertet wurden (Median: 64,3%), erzielten die anderen Domänen signifikant schlechtere Ergebnisse (padj.<0,001): Die Lesbarkeit der dargestellten Informationen ist als schwierig einzustufen (Median: 40,0%). Auch der Informationsumfang (Median: 11,5%) sowie die allgemeine Qualität und Zuverlässigkeit (Median: 16,7%) ist gering. Zwischen den verschiedenen Anbietern zeigten sich Differenzen im Gesamtscore und hinsichtlich der technischen und funktionellen Aspekte sowie des Informationsumfangs (p≤0,005): Websites von Fachgesellschaften, öffentlichen Einrichtungen oder Versicherungsgesellschaften erzielten die höchsten Scores. Auch praxisspezifische Parameter privater Zahnarztpraxen beeinflussten die Lesbarkeit der dargestellten Informationen: Websites, bei denen Zahnärzt*innen erst vor kürzerer Zeit ihre Examination erlangten, sind leichter zu lesen (p=0,012; B=0,24 pro Jahr), während Websites ausländischer Praxen (p=0,036; B=-6,64) oder von Zahnärzt*innen, die Mitglied in mindestens einer Fachgesellschaft sind, schwieriger zu lesen sind (p=0,049; B=-3,55).
Insgesamt wird deutlich, dass eine Weiterentwicklung der Informationsqualität von Websites und YouTube-Videos über erosive Zahnartsubstanzdefekte notwendig ist, damit diese als informative und zuverlässige Informationsquelle genutzt werden können. Es sollten mehr Zahnärzt*innen dazu ermutigt werden, Patient*inneninformationen über erosive Zahnhartsubstanzdefekte auf ihren Websites zur Verfügung zu stellen, sodass Patient*innen die Informationsbeschaffung erleichtert wird.Due to the ongoing digitalization process, the number of Internet users searching for health information online is constantly increasing. As tooth decay declines, erosive tooth wear are becoming a growing focus. However, it is currently unclear to what extent patients can reliably obtain information about erosive tooth wear on the Internet.
As part of the study, German-language content (websites and YouTube videos) from various providers was identified using a systematic search strategy. Demographic data and practice-specific parameters were extracted from the providers, and the scope of information in the content was evaluated with regard to erosive tooth wear. In addition, the quality of the websites was examined on the basis of various domains: technical and functional aspects (LIDA), readability (FLESCH), general quality, and reliability as a source of information (DISCERN). The statistical comparison between the different domains, the different providers, and the different content was performed using the Friedman test, Kruskal-Wallis tests, and Wilcoxon test. The potential influence of practice-specific parameters was examined using generalized linear models. The study included 231 websites and 7 YouTube videos. The majority of the websites included are provided by private dental offices, followed by corporate dental offices and dental societys. While technical and functional aspects received the highest ratings (median: 64.3%), the other domains scored significantly lower (padj.<0.001): The readability of the information presented is considered difficult (median: 40.0%). The scope of information (median: 11.5%) and the overall quality and reliability (median: 16.7%) are also low. There were differences between the various providers in terms of overall score and with regard to technical and functional aspects as well as the scope of information (p≤0.005): Websites of dental societies, dental regulatory bodies, public bodies, or insurance companies achieved the highest scores. Practice-specific parameters of private dental offices also influenced the readability of the information presented: websites where dentists had only recently obtained their examination are easier to read (p=0.012; B=0.24 per year), while websites of foreign practices (p=0.036; B=-6.64) or dentists who are members of at least one dental society are more difficult to read (p=0.049; B=-3.55). Overall, it is clear that the quality of information provided on websites and YouTube videos about erosive tooth wear needs to be improved so that they can be used as informative and reliable sources of information. More dentists should be encouraged to provide patient information about erosive tooth wear on their websites to make it easier for patients to obtain information.2026-04-0