Feasibility and Short-Term SpO2/FiO2 Changes in Hospitalized Adults with COVID-19 Pneumonia after Chest Physiotherapy with Threshold PEP Valve: A Cross-Sectional Study.

BACKGROUND: One of the main features of COVID-19 pneumonia is hypoxemic acute respiratory failure (ARF), often requiring ventilatory support. The influence of chest physiotherapy in patients with ARF is not extensively studied. The aim of the study was to analyze the short-time effects of chest physiotherapy using a 10 cm H2O threshold valve in patients with COVID-19 and ARF. Methods; Quasi-experimental cross-sectional study, in hospitalized patients from March to May 2020. The fractions of inspired oxygen, oxygen saturation, heart rate, respiratory rate and dyspnea were collected before and after the starting session (day 1) and after the 5th day of therapy. RESULTS: The final sample size included 125 patients. Significant differences (p < 0.01) were found in the pre-post intervention SpO2/FiO2 ratio (250 ± 88.4 vs. 275.6 ± 97.5, p < 0.001), reaching 354.4 ± 110.2 after 5 days of therapy (p < 0.001 with respect to the baseline). The respiratory and heart rate dyspnea level did not change during the intervention. In patients needing FiO2 > 0.4, the SpO2/FiO2 ratio improvement was higher than in patients with milder severity (46.85 ± 77.69, p < 0.01). CONCLUSIONS: Chest physiotherapy with a 10 cm H2O threshold valve seems to be a safe and tolerated intervention with short-term improvement in oxygenation in patients with COVID-19 pneumonia.

Extrusion of Porous Protein-Based Polymers and Their Liquid Absorption Characteristics.

The production of porous wheat gluten (WG) absorbent materials by means of extrusion processing is presented for the future development of sustainable superabsorbent polymers (SAPs). Different temperatures, formulations, and WG compositions were used to determine a useful protocol that provides the best combination of porosity and water swelling properties. The most optimal formulation was based on 50 wt.% WG in water that was processed at 80 °C as a mixture, which provided a porous core structure with a denser outer shell. As a green foaming agent, food-grade sodium bicarbonate was added during the processing, which allowed the formation of a more open porous material. This extruded WG material was able to swell 280% in water and, due to the open-cell structure, 28% with non-polar limonene. The results are paving the way towards production of porous bio macromolecular structures with high polar/non-polar liquid uptake, using extrusion as a solvent free and energy efficient production technique without toxic reagents.

Hepatitis B virus X protein stimulates gene expression selectively from extrachromosomal DNA templates.

UNLABELLED: Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cancer development. HBV encodes the hepatitis B virus X (HBx) protein that promotes transcription of the viral episomal DNA genome by the host cell RNA polymerase II. Here we provide evidence that HBx accomplishes this task by a conserved and unusual mechanism. Thus, HBx strongly stimulates expression of transiently transfected reporter constructs, regardless of the enhancer and promoter sequences. This activity invariably requires HBx binding to the cellular UV-damaged DDB1 E3 ubiquitin ligase, suggesting a common mechanism. Unexpectedly, none of the reporters tested is stimulated by HBx when integrated into the chromosome, despite remaining responsive to their cognate activators. Likewise, HBx promotes gene expression from the natural HBV episomal template but not from a chromosomally integrated HBV construct. The same was observed with the HBx protein of woodchuck HBV. HBx does not affect nuclear plasmid copy number and functions independently of CpG dinucleotide methylation. CONCLUSION: We propose that HBx supports HBV gene expression by a conserved mechanism that acts specifically on episomal DNA templates independently of the nature of the cis-regulatory sequences. Because of its uncommon property and key role in viral transcription, HBx represents an attractive target for new antiviral therapies.

A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery.

The cullin 4-DNA-damage-binding protein 1 (CUL4-DDB1) ubiquitin ligase machinery regulates diverse cellular functions and can be subverted by pathogenic viruses. Here we report the crystal structure of DDB1 in complex with a central fragment of hepatitis B virus X protein (HBx), whose DDB1-binding activity is important for viral infection. The structure reveals that HBx binds DDB1 through an alpha-helical motif, which is also found in the unrelated paramyxovirus SV5-V protein despite their sequence divergence. Our structure-based functional analysis suggests that, like SV5-V, HBx captures DDB1 to redirect the ubiquitin ligase activity of the CUL4-DDB1 E3 ligase. We also identify the alpha-helical motif shared by these viral proteins in the cellular substrate-recruiting subunits of the E3 complex, the DDB1-CUL4-associated factors (DCAFs) that are functionally mimicked by the viral hijackers. Together, our studies reveal a common yet promiscuous structural element that is important for the assembly of cellular and virally hijacked CUL4-DDB1 E3 complexes.

Hepatitis B virus X protein affects S phase progression leading to chromosome segregation defects by binding to damaged DNA binding protein 1.

UNLABELLED: Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), but its role in the transformation process remains unclear. HBV encodes a small protein, known as HBx, which is required for infection and has been implicated in hepatocarcinogenesis. Here we show that HBx induces lagging chromosomes during mitosis, which in turn leads to formation of aberrant mitotic spindles and multinucleated cells. These effects require the binding of HBx to UV-damaged DNA binding protein 1 (DDB1), a protein involved in DNA repair and cell cycle regulation, and are unexpectedly attributable to HBx interfering with S-phase progression and not directly with mitotic events. HBx also affects S-phase and induces lagging chromosomes when expressed from its natural viral context and, consequently, exhibits deleterious activities in dividing, but not quiescent, hepatoma cells. CONCLUSION: In addition to its reported role in promoting HBV replication, the binding of HBx to DDB1 may induce genetic instability in regenerating hepatocytes and thereby contribute to HCC development, thus making this HBV-host protein interaction an attractive target for new therapeutic intervention.