That Sinking Feeling: People with Disabilities in Hospital Wards

This study examined the experiences of people with disabilities in general hospitals. Specifically, we identified and analysed the barriers and difficulties that people with disabilities face while hospitalised. Using qualitative methods, our findings were based on a combination of in-depth interviews and a focus group with twenty inpatients in total. Three major barriers to proper care arose from the transcripts: inaccessibility, practitioners’ lack of medical knowledge, and negative stereotypes. While some of the findings reinforce existing knowledge about barriers faced by people with disabilities, some address barriers that have not yet been investigated with qualitative instruments, such as lack of specific medical knowledge. In addition, the findings suggest the need to refer separately to physical and service accessibility, the latter including human service and communication. Practical recommendations include the need to upgrade healthcare accessibility regulations and ways to help people with disabilities receive equal health services during hospitalisation

Enhanced production yields of rVSV-SARS-CoV-2 vaccine using Fibra-Cel® macrocarriers

The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension. However, the titers were limited by both the carrier surface area and shear forces. Here, we describe the development of a bioprocess for rVSV-ΔG-spike production in serum-free Vero cells using porous Fibra-Cel® macrocarriers in fixed-bed BioBLU®320 5p bioreactors, leading to high-end titers. We identified core factors that significantly improved virus production, such as the kinetics of virus production, the use of macrospargers for oxygen supply, and medium replenishment. Implementing these parameters, among others, in a series of GMP production processes improved the titer yields by at least two orders of magnitude (2e9 PFU/mL) over previously reported values. The developed process was highly effective, repeatable, and robust, creating potent and genetically stable vaccine viruses and introducing new opportunities for application in other viral vaccine platforms

Cellular Levels of Signaling Factors Are Sensed by β-actin Alleles to Modulate Transcriptional Pulse Intensity

The transcriptional response of β-actin to extra-cellular stimuli is a paradigm for transcription factor complex assembly and regulation. Serum induction leads to a precisely timed pulse of β-actin transcription in the cell population. Actin protein is proposed to be involved in this response, but it is not known whether cellular actin levels affect nuclear β-actin transcription. We perturbed the levels of key signaling factors and examined the effect on the induced transcriptional pulse by following endogenous β-actin alleles in single living cells. Lowering serum response factor (SRF) protein levels leads to loss of pulse integrity, whereas reducing actin protein levels reveals positive feedback regulation, resulting in elevated gene activation and a prolonged transcriptional response. Thus, transcriptional pulse fidelity requires regulated amounts of signaling proteins, and perturbations in factor levels eliminate the physiological response, resulting in either tuning down or exaggeration of the transcriptional pulse

Azithromycin and Sildenafil May Have Protective Effects on Retinal Ganglion Cells via Different Pathways: Study in a Rodent Microbead Model

Decreased blood flow to the optic nerve (ON) and neuroinflammation are suggested to play an important role in the pathophysiology of glaucoma. This study investigated the potential neuroprotective effect of azithromycin, an anti-inflammatory macrolide, and sildenafil, a selective phosphodiesterase-5 inhibitor, on retinal ganglion cell survival in a glaucoma model, which was induced by microbead injection into the right anterior chamber of 50 wild-type (WT) and 30 transgenic toll-like receptor 4 knockout (TLR4KO) mice. Treatment groups included intraperitoneal azithromycin 0.1 mL (1 mg/0.1 mL), intravitreal sildenafil 3 µL, or intraperitoneal sildenafil 0.1 mL (0.24 μg/3 µL). Left eyes served as controls. Microbead injection increased intraocular pressure (IOP), which peaked on day 7 in all groups and on day 14 in azithromycin-treated mice. Furthermore, the retinas and ON of microbead-injected eyes showed a trend of increased expression of inflammatory- and apoptosis-related genes, mainly in WT and to a lesser extent in TLR4KO mice. Azithromycin reduced the BAX/BCL2 ratio, TGFβ, and TNFα levels in the ON and CD45 expression in WT retina. Sildenafil activated TNFα-mediated pathways. Both azithromycin and sildenafil exerted a neuroprotective effect in WT and TLR4KO mice with microbead-induced glaucoma, albeit via different pathways, without affecting IOP. The relatively low apoptotic effect observed in microbead-injected TLR4KO mice suggests a role of inflammation in glaucomatous damage