Nanomechanics of the endothelial glycocalyx in experimental sepsis

The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal side of the endothelium, regulates vascular adhesiveness and permeability. Although central to the pathophysiology of vascular barrier dysfunction in sepsis, glycocalyx damage has been generally understudied, in part because of the aberrancy of in vitro preparations and its degradation during tissue handling. The aim of this study was to analyze inflammation-induced damage of the eGC on living endothelial cells by atomic-force microscopy (AFM) nanoindentation technique. AFM revealed the existence of a mature eGC on the luminal endothelial surface of freshly isolated rodent aorta preparations ex vivo, as well as on cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM detected a marked reduction in glycocalyx thickness (266 ± 12 vs. 137 ± 17 nm, P<0.0001) and stiffness (0.34 ± 0.03 vs. 0.21 ± 0.01 pN/mn, P<0.0001) in septic mice (1 mg E. coli lipopolysaccharides (LPS)/kg BW i.p.) compared to controls. Corresponding in vitro experiments revealed that sepsis-associated mediators, such as thrombin, LPS or Tumor Necrosis Factor-α alone were sufficient to rapidly decrease eGC thickness (-50%, all P<0.0001) and stiffness (-20% P<0.0001) on HPMEC. In summary, AFM nanoindentation is a promising novel approach to uncover mechanisms involved in deterioration and refurbishment of the eGC in sepsis

Clinical outcomes in patients relapsed/refractory after ≥2 prior lines of therapy for follicular lymphoma: A systematic literature review and meta-analysis

BACKGROUND: Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapy (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT identified through systematic literature review. METHODS: Eligible studies included comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT published prior to 31st May 2021. Prior LOT must have included an anti-CD20 monoclonal antibody and an alkylating agent, in combination or separately. Overall response rate (ORR) and complete response (CR) were estimated using inverse-variance weighting with Freeman-Tukey double-arcsine transformations. Kaplan-Meier (KM) curves for progression-free survival (PFS) and overall survival (OS) estimated by reconstructing digitized curves using the Guyot algorithm, and survival analyses were conducted, stratified by ≥2 prior LOT and ≥ 3 prior LOT groups (as defined in the source material). Restricting the analyses to the observational cohorts was investigated as a sensitivity analysis. RESULTS: The analysis-set included 20 studies published between 2014 and 2021. Studies were primarily US and/or European based, with the few exceptions using treatments approved in US/Europe. The estimated ORR was 58.47% (95% confidence interval [CI]: 51.13-65.62) and proportion of patients with CR was 19.63% (95% CI: 15.02-24.68). The median OS among those ≥2 prior LOT was 56.57 months (95% CI: 47.8-68.78) and median PFS was 9.78 months (95% CI: 9.01-10.63). The 24-month OS decreased from 66.50% in the ≥2 prior LOT group to 59.51% in the ≥3 prior LOT group, with a similar trend in PFS at 24-month (28.42% vs 24.13%). CONCLUSIONS: This study found that few r/r FL patients with ≥2 prior LOT achieve CR, and despite some benefit, approximately 1/3 of treated patients die within 24 months. The shorter median PFS with increasing prior LOT suggest treatment durability is suboptimal in later LOT. These findings indicate that patients are underserved by treatments currently available in the US and Europe

A hydrogen beam to characterize the ASACUSA antihydrogen hyperfine spectrometer

The antihydrogen programme of the ASACUSA collaboration at the antiproton decelerator of CERN focuses on Rabi-type measurements of the ground-state hyperfine splitting of antihydrogen for a test of the combined Charge-Parity-Time symmetry. The spectroscopy apparatus consists of a microwave cavity to drive hyperfine transitions and a superconducting sextupole magnet for quantum state analysis via Stern-Gerlach separation. However, the small production rates of antihydrogen forestall comprehensive performance studies on the spectroscopy apparatus. For this purpose a hydrogen source and detector have been developed which in conjunction with ASACUSA's hyperfine spectroscopy equipment form a complete Rabi experiment. We report on the formation of a cooled, polarized, and time modulated beam of atomic hydrogen and its detection using a quadrupole mass spectrometer and a lock-in amplification scheme. In addition key features of ASACUSA's hyperfine spectroscopy apparatus are discussed.

Evolution of the fishtail-effect in pure and Ag-doped MG-YBCO

We report on magnetic measurements carried out in a textured YBa$_2$Cu$_3$O$_{7-\delta}$ and YBa$_2$(Cu$_{1-x}$Ag$_x$)$_3$O$_{7-\delta}$ (at $x \approx$ 0.02) crystals. The so-called fishtail-effect (FE) or second magnetization peak has been observed in a wide temperature range 0.4~$<T/T_c<$~0.8 for $\textbf{H}\parallel c$. The origin of the FE arises for the competition between surface barrier and bulk pinning. This is confirmed in a non-monotonically behavior of the relaxation rate $R$. The value $H_{max}$ for Ag-doped crystals is larger than for the pure one due to the presence of additional pinning centers, above all on silver atoms.Comment: 6 pages, 6 figure

Whole-body vibration training induces hypertrophy of the human patellar tendon

I Brage finner du siste tekst-versjon av artikkelen, og den kan inneholde ubetydelige forskjeller fra forlagets pdf-versjon. Forlagets pdf-versjon finner du på onlinelibrary.wiley.com / In Brage you'll find the final text version of the article, and it may contain insignificant differences from the journal's pdf version. The definitive version is available at onlinelibrary.wiley.comAnimal studies suggest that regular exposure to whole-body vibration (WBV) induces an anabolic response in bone and tendon. However, the effects of this type of intervention on human tendon properties and its influence on the muscle-tendon unit function have never been investigated. The aim of this study was to investigate the effect of WBV training on the patellar tendon mechanical, material and morphological properties, the quadriceps muscle architecture and the knee extension torque–angle relationship. Fifty-five subjects were randomized into either a vibration, an active control, or an inactive control group. The active control subjects performed isometric squats on a vibration platform without vibration. Muscle and tendon properties were measured using ultrasonography and dynamometry. Vibration training induced an increase in proximal (6.3%) and mean (3.8%) tendon cross-sectional area, without any appreciable change in tendon stiffness and modulus or in muscle architectural parameters. Isometric torque at a knee angle of 90° increased in active controls (6.7%) only and the torque–angle relation remained globally unchanged in all groups. The present protocol did not appreciably alter knee extension torque production or the musculo-tendinous parameters underpinning this function. Nonetheless, this study shows for the first time that WBV elicits tendon hypertrophy in humans.Seksjon for fysisk prestasjonsevne / Department of Physical Performanc

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports