GC-MS analysis of phytoconstituents from Ruellia prostrata and Senna tora and identification of potential anti-viral activity against SARS-CoV-2

SARS-CoV-2 is an etiologic agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. The virus has rapidly extended globally and taken millions of lives due to the unavailability of therapeutics candidates against the virus. Till now, no specific drug candidates have been developed that can prevent or treat infections caused by the pathogen. The main protease (M^pro) of the SARS-CoV-2 plays a pivotal role in mediating viral replication and mechanistically inhibition of the protein can hinder the replication and infection process of the virus. Therefore, the study aimed to identify the natural bioactive compounds against the virus that can block the activity of the M^pro and subsequently block viral infections. Initially, a total of 96 phytochemicals from Ruellia prostrata Poir. and Senna tora (L.) Roxb. plants were identified through the gas chromatography-mass spectrometry (GC-MS) analytical method. Subsequently, the compounds were screened through molecular docking, absorption, distribution, metabolism, excretion (ADME), toxicity (T), and molecular dynamics (MD) simulation approach. The molecular docking method initially identified four molecules having a PubChem CID: 70825, CID: 25247358, CID: 54685836 and, CID: 1983 with a binding affinity ranging between −6.067 to −6.53 kcal mol⁻¹ to the active site of the target protein. All the selected compounds exhibit good pharmacokinetics and toxicity properties. Finally, the four compounds were further evaluated based on the MD simulation methods that confirmed the binding stability of the compounds to the targeted protein. The computational approaches identified the best four compounds CID: 70825, CID: 25247358, CID: 54685836 and, CID: 1983 that can be developed as a treatment option of SARS-CoV-2 disease-related complications. Although, experimental validation is suggested for further evaluation of the work.

Protease (M^pro) of SARS-CoV-2 has been identified as being able to hinder the replication process of the virus. Using GC-MS analytical methods, phytochemicals were identified from different medicinal plants that resulted in inhibitory activity of the molecules against M^pro.     

A Study on the Mechanical Characteristics of Glass and Nylon Fiber Reinforced Peach Shell Lightweight Concrete

In the current study, the utilization of glass and nylon fibers in various percentages are added to enhance the mechanical performance of peach shell lightweight concrete. Glass and nylon fibers were added at 2%, 4%, 6%, and 8% by cement weight. The results showed that, as we added the glass and nylon fibers, the density of peach shell concrete was reduced by 6.6%, and the compressive, split tensile and flexural strength were enhanced by 10.20%, 60.1%, and 63.49%. The highest strength that was obtained in compressive, split tensile, and flexural strength at 56 days was 29.4 MPa, 5.2 MPa, and 6.3 MPa, respectively, with 6% of glass fiber in peach shell concrete. Mechanical test results showed that post-failure toughness and modulus of elasticity of peach shell concrete is enhanced with the utilization of fibers. To verify our lab results, a statistical analysis, such as response surface methodology, was performed to make a statistical model, it was confirmed by both lab results and statistical analysis that the mechanical performance of peach shell concrete could be significantly improved by adding glass fibers as compared to nylon fibers. With the use of fibers, the water absorption and porosity were slightly increased. Hence, the glass and nylon fibers can be used to improve the peach shell concrete mechanical properties to make concrete eco-friendly, sustainable, and lightweight.     

Effect of dexamethasone on the frequency of postdural puncture headache after spinal anesthesia for cesarean section: a double-blind randomized clinical trial

In this study, we evaluated the effect of dexamethasone used as a prophylaxis for nausea and vomiting on the incidence of postdural puncture headache (PDPH) in pregnant women receiving spinal anesthesia for cesarean section. In a prospective, randomized, double-blind, placebo-controlled study, 372 women under spinal anesthesia received 8?mg of dexamethasone or placebo intravenously just after the umbilical cord was clamped. The rate of PDPH and correlated risk factors were evaluated. The prevalence of nausea and vomiting in the dexamethasone and placebo groups was 54.4 and 51.7?%, respectively. There was no statistically meaningful difference between the results (P value?=?0.673). The overall incidence rate of PDPH was 10.8?%, with 28 cases from the dexamethasone group compared with 11 subjects from the placebo group (P value?=?0.006). This effect was most prominent on the first day (P value?=?0.046) and disappeared on the second day after spinal anesthesia (P value?=?0.678). Prophylactic treatment with 8?mg of dexamethasone not only increases the severity and incidence of PDPH, but is also ineffective in decreasing the prevalence of intra-operative nausea and vomiting during cesarean section. The treatment is a significant risk factor for the development of PDPH.     

Dose-related effects of hyperoxia on the lung inflammatory response in septic rats

We evaluated the effects of hyperoxia on pulmonary inflammatory changes in sepsis induced by cecal ligation and puncture (CLP) in rats. Seven groups were studied: sham-operated rats breathing air for 20 or 48 h; CLP breathing air for 20 or 48 h; and CLP + 100% oxygen for 20 h, or 70% oxygen for 48 h, or 100% oxygen intermittently (6 h/d) for 48 h. Video microscopy was used to monitor lung macromolecular leak, microvascular flow velocity, and shear rates, and lung morphometry was used for leukocyte infiltration and solid tissue area. Cell counts, tumor necrosis factor α, and nitrites were determined in peripheral blood and lung lavage fluid. Expression of adhesion molecules in blood leukocytes was evaluated by flow cytometry. Cecal ligation and puncture induced inflammation manifested in leukopenia, left shift, thrombocytopenia, increased expression of L selectin and CD11, increased serum and lavage fluid tumor necrosis factor α and leukocytes, and increased lung tissue area, macromolecular leak, and sequestration of leukocytes. Inhalation of 100% oxygen for 20 h increased nitrites (P < 0.01) and decreased leukocyte count in lavage fluid (P < 0.05) and attenuated lung macromolecular leak and changes in solid tissue area (P < 0.01). Inhalation of 70% oxygen (48 h) attenuated expression of adhesion molecules (P < 0.001) but failed to attenuate markers of lung inflammation. In contrast, intermittent 100% oxygen exerted favorable effects on markers of inflammation, attenuated leukocyte expression of L selectin and CD11 (P < 0.01), decreased pulmonary sequestration of leukocytes (P < 0.001), and ameliorated changes in macromolecular leak (P < 0.01) and lung solid tissue area (P < 0.05). Our data support the beneficial effects of safe subtoxic regimens of normobaric hyperoxia on the systemic and pulmonary inflammatory response following CLP.     

Biallelic TMEM260 variants cause truncus arteriosus,with or without renal defects

Only two families have been reported with biallelic TMEM260 variants segregating with structural heart defects and renal anomalies syndrome (SHDRA). With a combination of genome, exome sequencing and RNA studies, we identified eight individuals from five families with biallelic TMEM260 variants. Variants included one multi-exon deletion, four nonsense/frameshifts, two splicing changes and one missense change. Together with the published cases, analysis of clinical data revealed ventricular septal defects (12/12), mostly secondary to truncus arteriosus (10/12), elevated creatinine levels (6/12), horse-shoe kidneys (1/12) and renal cysts (1/12) in patients. Three pregnancies were terminated on detection of severe congenital anomalies. Six patients died between the ages of 6 weeks and 5 years. Using a range of stringencies, carrier frequency for SHDRA was estimated at 0.0007–0.007 across ancestries. In conclusion, this study confirms the genetic basis of SHDRA, expands its known mutational spectrum and clarifies its clinical features. We demonstrate that SHDRA is a severe condition associated with substantial mortality in early childhood and characterised by congenital cardiac malformations with a variable renal phenotype.     

Pharmacoenvironmentology – a component of pharmacovigilance

According to WHO, Pharmacovigilance activities are done to monitor detection, assessment, understanding and prevention of any obnoxious adverse reactions to drugs at therapeutic concentration on animal and human beings. However, there is also a growing focus among scientists and environmentalists about the impact of drugs on environment and surroundings. The existing term 'Ecopharmacology' is too broad and not even defined in a clear manner. The term 'Pharmacoenvironmentology' seeks to deal with the environmental impact of drugs given to humans and animals at therapeutic doses.     

Primary extradural hydatid cyst associated with nephrotic syndrome in a pediatric patient

Background  

Primary intracranial extradural hydatid cyst is a very rare entity. Overlying bony erosion and extension of an extradural hydatid cyst into the scalp has never been described in literature. Association of nephrotic syndrome is described in pulmonary and hepatic hydatid cysts, but never reported in intracranial hydatidosis.