Klinische und arthrosonographische Überprüfung der Auswirkung von mechanischem Stress auf Enthesen bei aktiven Badmintonsportlern

1 Zusammenfassung Hintergrund und Ziele Die Psoriasisarthritis ist eine bedeutende Komorbidität der kutanen Psoriasis, die genaue Ursache ihrer Manifestation ist aber bis heute nicht abschließend geklärt. Eine zentrale Rolle wird dabei dem Auftreten von Enthesitiden zugeschrieben, welche neben Daktylitiden und Synovitiden ein entscheidendes differentialdiagnostisches Merkmal der Psoriasisarthritis darstellen. Aber auch die Ätiologie der Enthesitiden selbst ist noch weitestgehend unklar. Es existieren mehrere Hypothesen, die ihre Entstehung auf verschiedene Art zu erklären versuchen. Die derzeit vielversprechendste besagt, dass neben immunologischen Prozessen vor allem mechanischer Stress auf die Sehnenansätze die charakteristische Inflammation auslöst. Die Fragestellung der vorliegenden Arbeit ist, ob intensiver physikomechanischer Stress Auswirkungen auf Enthesen gesunder Probanden hat. Ziel ist es dabei, vor allem das Neuauftreten von Enthesitiden nach gezielter Belastung mittels klinischer Untersuchung und Ultraschall zu detektieren. Methode Bei insgesamt 32 Badmintonspielern erfolgte zunächst die Erhebung verschiedener demographischer Daten. Anschließend wurde jeweils vor und unmittelbar nach einem mindestens 45-minütigen Training eine klinische und arthrosonographische Untersuchung (B-Bild und Power-Doppler) von den Enthesen der Achillessehnen, Patellasehnen und Ellenbogen durchgeführt. Anschließend wurde der Vergleich der beiden Zeitpunkte sowie der dominanten zur nicht-dominanten Schlagseite angestellt. Ergebnisse Insgesamt wurden 32 Probanden (22 Männer, 10 Frauen) untersucht. Diese waren bereits 16,2 ± 10,1 Jahre im Badmintonsport aktiv. Die Untersuchung mittels Arthrosonographie fand schließlich an 192 Enthesen anhand eines angepassten Scores nach d’Agostino statt. Nur im Power-Doppler ergab sich hier eine signifikante Änderung der empirischen Gesamtwerte nach dem Training im Mixed Model (p=0,017), während diese im Grey-Scale nicht relevant waren (p=0,645). Von allen Unterschieden im Farbdoppler lagen 71,4% auf der dominanten Schlagseite. Schlussfolgerung Bei gesunden Probanden zeigt sich nach einer gezielten, mechanischen Belastung auf bestimmte Enthesen eine signifikante Zunahme des Farbdopplersignals. Somit erzielt bereits eine kurzfristige, physikomechanische Belastung Zeichen einer Enthesitis; in zukünftigen Untersuchungen ist es notwendig, zusätzlich psoriasisspezifische Faktoren in Populationen erkrankter Probanden genauer zu betrachten

Electron spin-lattice relaxation in solid ethanol: the effect of nitroxyl radical hydrogen bonding and matrix disorder

The electron spin-lattice relaxation of TEMPO and TEMPONE was measured at temperatures between 5 and 80 K in crystalline and glassy ethanol using X-band electron paramagnetic resonance spectroscopy. The experimental data at the lowest temperatures studied were explained in terms of electron-nuclear dipolar interaction between the paramagnetic center and the localized excitations, whereas at higher temperatures low-frequency vibrational modes from the host matrix and Raman processes should be considered. The strong impact of hydrogen bonding between the dopant molecule and ethanol host on the spin relaxation was observed in ethanol glass whereas in crystalline ethanol both paramagnetic guest molecules behaved similarly.Comment: 13 pages, 2 figures, 32 reference

Tocilizumab administration in cytokine release syndrome is associated with hypofibrinogenemia after chimeric antigen receptor T-cell therapy for hematologic malignancies

Chimeric antigen receptor (CAR-) T cell therapy causes serious side effects including cytokine release syndrome (CRS). CRS-related coagulopathy is associated with hypofibrinogenemia that is thus far considered the result of disseminated intravascular coagulation (DIC) and liver dysfunction. We investigated incidence and risk factors for hypofibrinogenemia in 41 consecutive adult patients with hematologic malignancies (median age 69 years, range 38-83 years) receiving CAR-T cell therapy between 01/2020 and 05/2023 at the University Medical Center Regensburg. CRS occurred in 93% of patients and was accompanied by hypofibrinogenemia already from CRS grade 1. Yet, DIC and liver dysfunction mainly occurred in severe CRS (≥ grade 3). After an initial increase during CRS, fibrinogen levels dropped after administration of tocilizumab in a dose dependent manner (r = -0.44, p = 0.004). In contrast, patients who did not receive tocilizumab had increased fibrinogen levels. Logistic regression analysis identified tocilizumab as an independent risk factor for hypofibrinogenemia (odds ratio = 486, p < 0.001). We thus hypothesize that fibrinogen synthesis in CRS is upregulated in an interleukin-6-dependent acute phase reaction compensating for CRS-induced consumption of coagulation factors. Tocilizumab inhibits fibrinogen upregulation resulting in prolonged hypofibrinogenemia. These observations provide novel insights into the pathophysiology of hypofibrinogenemia following CAR-T cell therapy and emphasize the need for close fibrinogen monitoring after tocilizumab treatment of CRS

Executive Function and Falls in Older Adults: New Findings from a Five-Year Prospective Study Link Fall Risk to Cognition

Background: Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk. Methodology/Main Results We longitudinally followed 256 community-living older adults (age: 76.4±4.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74–.98, p = .021), the attention index (RR: .84; CI: .75–.94, p = .002) and dual tasking gait variability (RR: 1.11; CI: 1.01–1.23; p = .027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p<0.02). Conclusions/Significance: These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk

ENDOR Spectroscopy and DFT Calculations: Evidence for the Hydrogen-Bond Network Within α2 in the PCET of E. coli Ribonucleotide Reductase

Escherichia coli class I ribonucleotide reductase (RNR) catalyzes the conversion of nucleotides to deoxynucleotides and is composed of two subunits: α2 and β2. β2 contains a stable di-iron tyrosyl radical (Y[subscript 122]•) cofactor required to generate a thiyl radical (C[subscript 439]•) in α2 over a distance of 35 Å, which in turn initiates the chemistry of the reduction process. The radical transfer process is proposed to occur by proton-coupled electron transfer (PCET) via a specific pathway: Y[subscript 122] ⇆ W[subscript 48][?] ⇆ Y[subscript 356] in β2, across the subunit interface to Y[subscript 731] ⇆ Y[subscript 730] ⇆ C[subscript 439] in α2. Within α2 a colinear PCET model has been proposed. To obtain evidence for this model, 3-amino tyrosine (NH2Y) replaced Y[subscript 730] in α2, and this mutant was incubated with β2, cytidine 5′-diphosphate, and adenosine 5′-triphosphate to generate a NH2Y730• in D2O. [[superscript 2]H]-Electron–nuclear double resonance (ENDOR) spectra at 94 GHz of this intermediate were obtained, and together with DFT models of α2 and quantum chemical calculations allowed assignment of the prominent ENDOR features to two hydrogen bonds likely associated with C[subscript 439] and Y[subscript 731]. A third proton was assigned to a water molecule in close proximity (2.2 Å O–H···O distance) to residue 730. The calculations also suggest that the unusual g-values measured for NH[subscript 2]Y[subscript 730]• are consistent with the combined effect of the hydrogen bonds to Cys[subscript 439] and Tyr[subscript 731], both nearly perpendicular to the ring plane of NH[subscript 2]Y[subscript 730]. The results provide the first experimental evidence for the hydrogen-bond network between the pathway residues in α2 of the active RNR complex, for which no structural data are available.National Institutes of Health (U.S.) (NIH GM29595

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

Calibration of the CMS hadron calorimeters using proton-proton collision data at root s=13 TeV

Methods are presented for calibrating the hadron calorimeter system of theCMSetector at the LHC. The hadron calorimeters of the CMS experiment are sampling calorimeters of brass and scintillator, and are in the form of one central detector and two endcaps. These calorimeters cover pseudorapidities vertical bar eta vertical bar ee data. The energy scale of the outer calorimeters has been determined with test beam data and is confirmed through data with high transverse momentum jets. In this paper, we present the details of the calibration methods and accuracy.Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.