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Photon propagation through an array of coupled waveguides arranged in various fractal patterns serves as a useful ‘optical simulator’ for revealing insights into quantum transport in complex scenarios.

Neuroimmune interactions may contribute to severe pain and regional inflammatory and autonomic signs in complex regional pain syndrome (CRPS), a posttraumatic pain disorder. Here, we investigated peripheral and central immune mechanisms in a translational passive transfer trauma mouse model of CRPS. Small plantar skin–muscle incision was performed in female C57BL/6 mice treated daily with purified serum immunoglobulin G (IgG) from patients with longstanding CRPS or healthy volunteers followed by assessment of paw edema, hyperalgesia, inflammation, and central glial activation. CRPS IgG significantly increased and prolonged swelling and induced stable hyperalgesia of the incised paw compared with IgG from healthy controls. After a short-lasting paw inflammatory response in all groups, CRPS IgG-injected mice displayed sustained, profound microglia and astrocyte activation in the dorsal horn of the spinal cord and pain-related brain regions, indicating central sensitization. Genetic deletion of interleukin-1 (IL-1) using IL-1αβ knockout (KO) mice and perioperative IL-1 receptor type 1 (IL-1R1) blockade with the drug anakinra, but not treatment with the glucocorticoid prednisolone, prevented these changes. Anakinra treatment also reversed the established sensitization phenotypewhen initiated 8 days after incision. Furthermore, with the generation of an IL-1β floxed(fl/fl) mouse line, we demonstrated that CRPS IgG-induced changes are in part mediated by microglia-derived IL-1β, suggesting that both peripheral and central inflammatory mechanisms contribute to the transferred disease phenotype. These results indicate that persistent CRPS is often contributed to by autoantibodies and highlight a potential therapeutic use for clinically licensed antagonists, such as anakinra, to prevent or treat CRPS via blocking IL-1 actions.

Most beekeepers worldwide use the same combs in their hives for many years, which can result in alterations in the inner volume of the comb cells. The objective of this survey using microcomputed tomography was to reveal developmental dis-orders caused by this beekeeping practice. The extent of the thickening of the wall of brood cells that occurs as a result of the long-term use of the combs was determined. This alteration resulted in a reduction in the inner volume of the comb cells, which had a signifi cant effect on the size of the pupae and possibly the health of the imagoes. The walls of the cells can be divided into two well-determined parts, which can be exactly visualized using micro-CT. In addition, the inner structure of the wall in the fi rst part of the cell was altered by very radio dense remains of cocoons. The material in the other part of the cell is less radio dense and as previously suggested is mainly wax. The decrease in the length, surface and volume of these cells adversely affected the developing pupae, which according to previous studies results in a reduction in the production of workers, colony strength and honey yield. The extent of the reduction in the body regions of pupae was on average 4.98%. Overall, the volume of the pupae that developed in these narrow comb cells were smaller by an average of 12.22%.

Pituitary adenylate cyclase–activating polypeptide (PACAP) is a naturally secreted signaling peptide and has important regulatory roles in the differentiation of the central nervous system and its absence results in disorders in femur development. PACAP has an important function in prevention of oxidative stress or mechanical stress in chondrogenesis but little is known about its function in bone regeneration. A new callus formation model was set to investigate its role in bone remodeling. Fracturing was 5 mm distal from the proximal articular surface of the tibia and the depth was 0.5 mm. Reproducibility of callus formation was investigated with CT 3, 7, and 21 days after the operation. Absence of PACAP did not alter the alkaline phosphatase (ALP) activation in PACAP KO healing process. In developing callus, the expression of collagen type I increased in wild-type (WT) and PACAP KO mice decreased to the end of healing process. Expression of the elements of BMP signaling was disturbed in the callus formation of PACAP KO mice, as bone morphogenic protein 4 (BMP4) and 6 showed an early reduction in bone regeneration. However, elevated Smad1 expression was demonstrated in PACAP KO mice. Our results indicate that PACAP KO mice show various signs of disturbed bone healing and suggest PACAP compensatory and fine tuning effects in proper bone regeneration.

Middle cerebral artery occlusion (MCAO) models show substantial variability in outcome, introducing uncertainties in the evaluation of treatment effects. Early outcome predictors would be essential for prognostic purposes and variability control. We aimed to compare apparent diffusion coefficient (ADC) MRI data obtained during MCAO and shortly after reperfusion for their potentials in acute-phase outcome prediction. Fifty-nine male rats underwent a 45-min MCAO. Outcome was defined in three ways: 21-day survival; 24 h midline-shift and neurological scores. Animals were divided into two groups: rats surviving 21 days after MCAO (survival group, n = 46) and rats dying prematurely (non-survival/NS group, n = 13). At reperfusion, NS group showed considerably larger lesion volume and lower mean ADC of the initial lesion site (p < 0.0001), while during occlusion there were no significant group differences. At reperfusion, each survival animal showed decreased lesion volume and increased mean ADC of the initial lesion site compared to those during occlusion (p < 10 –6 ), while NS group showed a mixed pattern. At reperfusion, lesion volume and mean ADC of the initial lesion site were significantly associated with 24 h midline-shift and neurological scores. Diffusion MRI performed soon after reperfusion has a great impact in early-phase outcome prediction, and it works better than the measurement during occlusion.

Reliable adaptation in Class II resin-based composite (RBC) restorations with margins on cementum remains challenging. This study compared the internal adaptation (IA) and closed porosity (CP) of three restorative strategies for such cavities, using either total-etch or self-etch adhesive approaches. Standardized box-only cavities were prepared on both proximal surfaces of 30 extracted molars, applying self-etch on mesial and total-etch on distal cavities. Group 1 used a layered microhybrid RBC; Group 2 used a flowable RBC base beneath a layered microhybrid RBC; and Group 3 used a thermoviscous RBC in a 4 mm bulk increment. Micro-computed tomography was employed to assess IA and CP. ANOVA, Tukey post hoc, and univariate analyses were used to evaluate group differences and the effects of adhesive/restorative strategies. Group 2 demonstrated the best adaptation (0.10%), whereas Group 3 exhibited the highest internal gap ratio (0.63%) and the lowest CP (p = 0.006). Total-etch adhesive significantly improved IA compared to self-etch (p < 0.001). These findings emphasize the impact of material selection and adhesive technique on the quality of restorations in cementum-located Class II cavities.

The development of in vitro investigation models could be important using sensitive and fast methods during formulation. Intranasal applied drugs (meloxicam, lamotrigine, and levodopa) avoid the gastrointestinal tract and can achieve higher bioavailability, therefore a penetration extent is a key property. In this study, the in vitro adaptability of a modified horizontal diffusion cell was tested by using these model active pharmaceutical ingredients (APIs). The special factors consisted of the volume of the chambers, the arrangement of the stirrers, the design of probe input for real-time analysis and decreased membrane area. Membranes were impregnated by isopropyl myristate and by using phosphate buffer to evaluate the effect of API hydrophilicity on the diffusion properties. The lipophilicity of the API was proportional to the penetration extent through isopropyl myristate-impregnated membranes compared with buffer-soaked membranes. After evaluating the arithmetic mean of standard relative deviations and the penetrated extent of APIs at 15 min, Metricel® could be suggested for levodopa and meloxicam, and Whatman™ for lamotrigine. The modified model is suitable for inline, real-time detection, at nasal conditions, using small volumes of phases, impregnated membrane, to monitor the diffusion of the drug and to determine its concentration in the acceptor and donor phases.

State selective protocols, like entanglement purification, lead to an essentially non-linear quantum evolution, unusual in naturally occurring quantum processes. Sensitivity to initial states in quantum systems, stemming from such non-linear dynamics, is a promising perspective for applications. Here we demonstrate that chaotic behaviour is a rather generic feature in state selective protocols: exponential sensitivity can exist for all initial states in an experimentally realisable optical scheme. Moreover, any complex rational polynomial map, including the example of the Mandelbrot set, can be directly realised. In state selective protocols, one needs an ensemble of initial states, the size of which decreases with each iteration. We prove that exponential sensitivity to initial states in any quantum system has to be related to downsizing the initial ensemble also exponentially. Our results show that magnifying initial differences of quantum states (a Schrödinger microscope) is possible; however, there is a strict bound on the number of copies needed.

Iterated quantum protocols with measurement-based selection lead to deterministic chaos for the evolving pure state representing an ensemble of qubits. Deterministic chaos for the pure quantum state may lead to ergodic evolution in the sense that initial states from any small area on the Bloch sphere will cover the whole sphere after a finite number of iterations. We realize two steps of an ergodic protocol in a photonic experiment, where initial qubit states are encoded in the polarization and path degrees of freedom of down-converted photons stemming from a parametric process. We numerically analyze the effect of noise on the time evolution and show that the protocol, described by a Lattès map, remains quasi-ergodic for any initial state if the initial noise is small. Tomographic reconstruction of the quantum states throughout the evolution is consistent with simulations and thus demonstrates ergodicity of the quantum dynamics.

The coronavirus disease (COVID-19) pandemic caused unprecedented research activity all around the world but publications from Central-Eastern European countries remain scarce. Therefore, our aim was to characterise the features of the pandemic in the intensive care units (ICUs) among members of the SepsEast (Central-Eastern European Sepsis Forum) initiative. We conducted a retrospective, international, multicentre study between March 2020 and February 2021. All adult patients admitted to the ICU with pneumonia caused by COVID-19 were enrolled. Data on baseline and treatment characteristics, organ support and mortality were collected. Eleven centres from six countries provided data from 2139 patients. Patient characteristics were: median 68, [IQR 60–75] years of age; males: 67%; body mass index: 30.1 [27.0–34.7]; and 88% comorbidities. Overall mortality was 55%, which increased from 2020 to 2021 (p = 0.004). The major causes of death were respiratory (37%), cardiovascular (26%) and sepsis with multiorgan failure (21%). 1061 patients received invasive mechanical ventilation (mortality: 66%) without extracorporeal membrane oxygenation (n = 54). The rest of the patients received non-invasive ventilation (n = 129), high flow nasal oxygen (n = 317), conventional oxygen therapy (n = 122), as the highest level of ventilatory support, with mortality of 50%, 39% and 22%, respectively. This is the largest COVID-19 dataset from Central-Eastern European ICUs to date. The high mortality observed especially in those receiving invasive mechanical ventilation renders the need of establishing national–international ICU registries and audits in the region that could provide high quality, transparent data, not only during the pandemic, but also on a regular basis.