Viral anti-inflammatory serpin reduces immuno-coagulopathic pathology in SARS-CoV-2 mouse models of infection.

SARS-CoV-2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti-viral drugs and monoclonal antibodies reduce early COVID-19 severity, but treatments for late-stage immuno-thrombotic syndromes and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases. The myxoma virus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic, and complement proteases as a self-defense strategy to combat clearance. Serp-1 is effective in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 as a therapy for immuno-coagulopathic complications during ARDS. Treatment with PEGSerp-1 in two mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved outcomes. PEGSerp-1 significantly reduced M1 macrophages in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR), thrombotic proteases, and complement membrane attack complex (MAC). Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for severe viral ARDS, immuno-coagulopathic responses, and Long COVID.

Self-ingestion of vasmol dye.

Vasmol, a commonly used hair dye, is becoming apparent as one of the major causes of suicidal poisoning in India. The toxic components in the dye include paraphenylenediamine, sodium ethylenediaminetetraacetic acid, resorcinol, and propylene glycol. Acute poisoning by consumption of dye leads to characteristic angioedema of the cervicofacial region along with multiorgan dysfunction. Early intervention with tracheostomy can be lifesaving in such cases and helps in preventing the morbidity and mortality associated with it.

Microbacterium Cluster EA Bacteriophages: Phylogenomic Relationships and Host Range Predictions.

Bacteriophages are being widely harnessed as an alternative to antibiotics due to the global emergence of drug-resistant pathogens. To guide the usage of these bactericidal agents, characterization of their host specificity is vital-however, host range information remains limited for many bacteriophages. This is particularly the case for bacteriophages infecting the Microbacterium genus, despite their importance in agriculture, biomedicine, and biotechnology. Here, we elucidate the phylogenomic relationships between 125 Microbacterium cluster EA bacteriophages-including members from 11 sub-clusters (EA1 to EA11)-and infer their putative host ranges using insights from codon usage bias patterns as well as predictions from both exploratory and confirmatory computational methods. Our computational analyses suggest that cluster EA bacteriophages have a shared infection history across the Microbacterium clade. Interestingly, bacteriophages of all sub-clusters exhibit codon usage preference patterns that resemble those of bacterial strains different from ones used for isolation, suggesting that they might be able to infect additional hosts. Furthermore, host range predictions indicate that certain sub-clusters may be better suited in prospective biotechnological and medical applications such as phage therapy.

Complete Genome Sequence of the Microbacterium Bacteriophage Chako.

We characterized the complete genome sequence of Chako, an obligate lytic bacteriophage with siphovirus morphology from subcluster EA1 that infects Microbacterium foliorum NRRL B-24224. Its 41.6-kb genome contains 62 putative protein-coding genes and is highly similar to that of bacteriophage HanSolo (99.26% nucleotide identity).

Correlation of Portal Vein Diameter as a Reflection of Portal Hypertension With Clinical and Laboratory Parameters in Chronic Liver Disease.

Chronic liver disease (CLD) patients develop portal hypertension which lead to complications like splenomegaly, ascites and esophageal varices. Portal hypertension is defined as hepatic venous pressure gradient more than 5mmHg, being invasive it is difficult to measure. Some studies show that increased portal vein diameter (PVD) on ultrasonography correlate with oesophageal varices and can indicate portal hypertension. Studies correlating PVD with other complications of portal hypertension like ascites and spleen size are lacking. Aim of this study was to correlate portal vein diameter with ascites, spleen size, thrombocytopenia and prognostic markers like Child-Turcotte Pugh (CTP) score and Model for End stage Liver Disease (MELD) score in Chronic liver disease patients. MATERIAL: This was a cross-sectional observational study of patients with Chronic liver disease conducted at tertiary care teaching hospital. All patient underwent clinical history, examination, blood testing and ultrasonography. Data collected was analysed by using statistical tests. OBSERVATION: Out of 97 CLD patients taken in study, the mean age of patients was 47.39 ± 12.64 year and majority were male (75.3%). Most common etiological factor was alcohol (in 53.7%). On clinical examination, 55.7% patients had pallor, 54.6% had icterus. Chest radiograph shows pleural effusion in 14.4% patients. Mean portal vein diameter was found to be 12.31 ± 2.71mm. Correlation coefficient of portal vein diameter with spleen size was 0.3 with p value of 0.004 suggesting a positive correlation. Parameters like thrombocytopenia, CTP score and MELD score correlation coefficient was -0.2(p-value: 0.066), 0.1(p value: 0.463) and 0.0(p-value: 0.725) respectively. The mean of PVD(mm) in ascites group was 12.43 and non ascites group was 11.92. Strength of association was 0.08 (Point Biserial correlation) indicating no association. CONCLUSION: Portal vein diameter had positive correlation with spleen size which is statistically significant in our study. No significant correlation was observed between PVD with ascites, thrombocytopenia, CTP score and MELD score.

Dengue Encephalitis: A Case Series on a Rare Presentation of Dengue Fever.

Neurological manifestations like encephalitis, especially hemorrhagic encephalitis, are rarely described in dengue fever (DF), and the gamut may affect any part of the central or peripheral nervous system. Herein, we report two cases from Northern India, presenting with fever and altered sensorium, subsequently diagnosed with DF. Imaging studies revealed hemorrhagic encephalitis in both of them but one of them had a grave outcome, unfolding the fatal nature of the disease. The report enlightens DF as an unusual etiology of encephalitis and the importance of considering the infirmity as a differential in patients with neurological manifestations.

Video Presentation of Myokymia in a Snakebite.

Patients with snakebites have highly variable presentations, and delayed diagnosis may lead to unfavorable outcomes. Here, we describe the case of a snakebite in a 23-year-old male who presented with myokymias. On management with mechanical ventilation and anti-snake venom, the patient improved and was discharged. The presence of myokymias may be an early clue to diagnosis and the need for mechanical ventilation in a patient with a snakebite.

Complete Genome Sequence of Microbacterium Bacteriophage Erla.

We characterized the complete genome sequence of Siphoviridae bacteriophage Erla, an obligatory lytic subcluster EA1 bacteriophage infecting Microbacterium foliorum NRRL B-24224, with a capsid width of 65 nm and a tail length of 112 nm. The 41.5-kb genome, encompassing 62 predicted protein-coding genes, is highly similar (99.52% identity) to that of bacteriophage Calix.

Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification.

Agent based models (ABM) were developed to numerically simulate the biological response to surgical vocal fold injury and repair at the physiological level. This study aimed to improve the representation of existing ABM through a combination of empirical and computational experiments. Empirical data of vocal fold cell populations including neutrophils, macrophages and fibroblasts were obtained using flow cytometry up to four weeks following surgical injury. Random Forests were used as a sensitivity analysis method to identify model parameters that were most influential to ABM outputs. Statistical Parameter Optimization Tool for Python was used to calibrate those parameter values to match the ABM-simulation data with the corresponding empirical data from Day 1 to Day 5 following surgery. Model performance was evaluated by verifying if the empirical data fell within the 95% confidence intervals of ABM outputs of cell quantities at Day 7, Week 2 and Week 4. For Day 7, all empirical data were within the ABM output ranges. The trends of ABM-simulated cell populations were also qualitatively comparable to those of the empirical data beyond Day 7. Exact values, however, fell outside of the 95% statistical confidence intervals. Parameters related to fibroblast proliferation were indicative to the ABM-simulation of fibroblast dynamics in final stages of wound healing.