orphological improvements that were easily identifiable during the 3rd month. Electrophysiological improvements were delayed only to become statistically significant in the 6th month. However, it has been shown that visual acuity and optical coherence tomography parameters alone may be insufficient for both the morphological and functional assessment of the retina.Bovine viral diarrhea virus-1 (BVDV-1, Pestivirus A) and BVDV-2 (Pestivirus B) have been clustered into 21 and 4 subtypes, respectively. This genetic diversity, in addition to the lack of consensus on which genomic region to use for BVDV subtyping, has resulted in conflicting classifications depending on the target analyzed. Here, we investigated which genes or UTRs would reproduce the phylogeny obtained by complete genome (CG) analyses. The study was carried out with 91 (BVDV-1) and 85 (BVDV-2) CG available on GenBank database. The viruses were subtyped by analyzing their CG, as well as their individual genes and UTRs (complete 3′ and 5’UTRs, and partial 5’UTR); and the phylogeny results were compared to each other. The sequences were aligned using the ClustalW multiple method (BioEdit Alignment Editor software, v.7.0.5.3) and the phylogenetic analyses were performed by the Maximum Likelihood method (MEGA-X software, v.10.2.4), with 1000 bootstrap replicates. The best analysis model for each gene/UTR was defined using the jModelTest software. The geodesic distance between the CG (reference) and individual genes/UTRs trees was also calculated (TreeCmp software, v.2.0). In general, 3’UTR-based analyses, followed by 5’UTR, presented the least reliable subtyping results. Regarding BVDV-1, phylogeny based on C, Erns, E1, E2, p7, NS2, NS3, NS4B, NS5A and NS5B was consistent with that of CG. In contrast, analyses performed with individual BVDV-2 genes showed at least one different clustering from the phylogeny based on the CG. After analyzing the geodesic distance between the CG and genes/UTRs trees, we observed that NS4B (for BVDV-1) and NS5A (BVDV-2) presented the closest topology and edge length to the CG analyses. Finally, comparing the phylogeny performed with the CG and the genes/UTRs, as well as the geodesic distance between them, we understand that NS4B and NS5A represent the most suitable targets for BVDV-1 and -2 subtyping, respectively, and may be considered in future phylogenetic studies.Structured hydrogel sheets offer the potential to mimic the mechanics and morphology of native cell environments in vitro; however, controlling the morphology of such sheets across multiple length scales to give cells consistent multi-dimensional cues remains challenging. Here, we demonstrate a simple two-step process based on sequential electrospinning and thermal wrinkling to create nanocomposite poly(oligoethylene glycol methacrylate)/cellulose nanocrystal hydrogel sheets with a highly tunable multi-scale wrinkled (micro) and fibrous (nano) morphology. By varying the time of electrospinning, rotation speed of the collector, and geometry of the thermal wrinkling process, the hydrogel nanofiber density, fiber alignment, and wrinkle geometry (biaxial or uniaxial) can be independently controlled. Adhered C2C12 mouse myoblast muscle cells display a random orientation on biaxially wrinkled sheets but an extended morphology (directed preferentially along the wrinkles) on uniaxially wrinkled sheets. While the nanoal interactions. Herein, we leverage a two-step process based on electrospinning and thermal wrinkling to prepare structured hydrogels with microscale wrinkles and nanoscale fibers. Fiber orientation/density and wrinkle geometry can be independently controlled during the electrospinning and thermal wrinkling processes respectively, demonstrating the flexibility of this technique for creating well-defined multiscale hydrogel structures. Finally, we show that while wrinkle geometry is the major determinant of cell alignment, nanofiber orientation also plays a role in this process.In cases of aortic stenosis, bioprosthetic heart valves (BHVs), with glutaraldehyde-fixed bovine pericardium leaflets (GLBP), are often implanted to replace the native diseased valve. Widespread use of BHVs, however, is restricted due to inadequate long-term durability, owing specifically to premature leaflet failure. Mechanical fatigue damage and calcification remain the primary leaflet failure modes, where glutaraldehyde treatment is known to accelerate calcification. The literature in this area is limited, with some studies suggesting mechanical damage increases calcification and others that they are independent degenerative mechanisms. In this study, specimens which were non-destructively pre-sorted according to collagen fibre architecture and uniaxially cyclically loaded until failure or 1 million cycles, were placed in an in vitro calcification solution. The weakest specimen group (those with fibres aligned perpendicular to the load) had statistically significantly higher volumes of calcification when crade GLBP specimens which were uniaxially cyclically loaded to failure or 1 million cycles, were placed in an in vitro calcification solution. MicroCT and SEM analysis showed that localised calcification levels varied spatially according to damage, where ruptured fibres offered additional calcium binding sites. Furthermore, specimens with a statistically significant lower fatigue life were associated with statistically significant higher calcification. This study revealed that mechanical damage drives calcification of GLBP. Non-destructive pre-screening of collagen fibres demonstrated that both the fatigue life and calcification potential of commercial-grade GLBP, are underpinned by the collagen fibre architecture.The present contribution analyses sanitary theatrical performances as a means of anti-tuberculosis propaganda in the early Soviet Union. Starting in the 1920s, sanitary theatrical performances were demonstrated in open-air theatres and clubhouses for workers and farmers. Since 1925, the newly founded Moscow Theatre for Sanitary Culture centrally managed the theatrical hygiene propaganda. It became a role model for other theatres of hygienic enlightenment and numerous sanitary amateur stages. Their anti-tuberculosis repertoire ranged from the so-called „mock trials” where a person or even Koch’s bacillus must stand trial for the spreading of tuberculosis, to „living newspapers” which used entertainment elements such as music or acrobatics to provide a mass audience with the hygiene knowledge. The contribution describes in which images, figures and actions knowledge about tuberculosis was presented on stage, which genre traditions and communicative instruments were used and which changing political implications those performances were based on. To achieve this goal, the archive sources, selected texts of theatrical performances, reports and reviews in daily press have been evaluated.With the increasing use of ketamine as an off-label treatment for depression and the recent FDA approval of (S)-ketamine for treatment-resistant depression, there is an increased need to understand the long-term safety profile of chronic ketamine administration. Of particular concern is the neurotoxicity previously observed in rat models following acute exposure to high doses of ketamine, broadly referred to as 'Olney’s lesions’. This type of toxicity presents as abnormal neuronal cellular vacuolization, followed by neuronal death and has been associated with ketamine’s inhibition of the N-methyl-d-aspartate receptor (NMDAR). In this study, a pharmacological and neuropathological analysis of ketamine, the potent NMDAR antagonist MK-801, and the ketamine metabolite (2R,6R)-hydroxynorketamine [(2R,6R)-HNK)] in rats is described following both single dose and repeat dose drug exposures. Ketamine dosing was studied up to 20 mg/kg intravenously for the single-dose neuropathology study and up to 60 mg/kg intraperitoneally for the multiple-dose neuropathology study. MK-801 dosing was studied up to 0.8 mg/kg subcutaneously for both the single and multiple-dose neuropathology studies, while (2R,6R)-HNK dosing was studied up to 160 mg/kg intravenously in both studies. These studies confirm dose-dependent induction of 'Olney’s lesions’ following both single dose and repeat dosing of MK-801. Ketamine exposure, while showing common behavioral effects, did not induce wide-spread Olney’s lesions. Treatment with (2R,6R)-HNK did not produce behavioral effects, toxicity or any evidence of Olney’s lesion formation. Based on these results, future NMDAR-antagonist neurotoxicity studies should strongly consider taking pharmacokinetics more thoroughly into account.Background CD47, a glycoprotein on red blood cell membranes, inhibits phagocytosis via interaction with signal regulatory protein α on phagocytes. Our previous research has demonstrated that blocking CD47 accelerates hematoma clearance and reduces brain injury after intracerebral hemorrhage. The current study investigated whether phagocytosis or erythrocyte CD47 impacts hematoma resolution and hydrocephalus development after intraventricular hemorrhage (IVH). Methods Adult (3-month-old) male Fischer 344 rats were intraventricularly injected with 200 μl autologous blood, mixed with either CD47 blocking antibody or isotype IgG, or 200 μl saline as control. In subgroups of CD47 blocking antibody treated rats, clodronate liposomes (to deplete microglia/monocyte-derived macrophages) or control liposomes were co-injected. Magnetic resonance imaging (MRI) was used to evaluate ventricular volume and intraventricular T2* lesion volume (estimating hematoma volume). The brains were harvested after 4 or 72 h for histology to evaluate phagocytosis. Results In adult male rats, CD47 blocking antibody alleviated hydrocephalus development by day 3. In addition, the CD47 blocking antibody reduced intraventricular T2* lesion and T2* non-hypointense lesion size after IVH through day 1 to day 3. Erythrophagocytosis was observed as soon as 4 h after IVH and was enhanced on day 3. Furthermore, intra-hematoma infiltration of CD68, heme oxygenase-1 and ferritin positive phagocytes were upregulated by CD47 blockade by day 3. Clodronate liposomes co-injection caused more severe hydrocephalus and weight loss. Conclusion Blocking CD47 in the hematoma accelerated hematoma clearance and alleviated hemolysis and hydrocephalus development after IVH, suggesting CD47 might be valuable in the future treatment for IVH.While several new translational strategies to enhance regrowth of peripheral axons have been identified, combined approaches with different targets are rare. Moreover, few have been studied after a significant delay when growth programs are already well established and regeneration-related protein expression has waned. Here we study two approaches, Rb1 (Retinoblastoma 1) knockdown that targets overall neuron plasticity, and near nerve insulin acting as a growth factor. Both are validated to boost regrowth only at the outset of regeneration. We show that local delivery of Rb1 siRNA alone, with electroporation to an area of prior sciatic nerve injury generated knockdown of Rb1 mRNA in ipsilateral lumbar dorsal root ganglia. While mice treated with Rb1-targeted siRNA, compared with scrambled control siRNA, starting 2 weeks after the onset of regeneration, had only limited behavioural or electrophysiological benefits, they had enhanced reinnervation of epidermal axons. We next confirmed that intrinsic Rb1 knockdown combined with exogenous insulin had dramatic synergistic impacts on the growth patterns of adult sensory neurons studied in vitro, prompting analysis of a combined approach in vivo.