Beta-Blockers and Their Current Role in Maternal and Neonatal Health: A Narrative Review of the Literature.

Beta-blockers are a class of medications that act on beta-adrenergic receptors and are categorized as cardio-selective and non-selective. They are principally used to treat cardiovascular conditions such as hypertension and arrhythmias. Beta-blockers have also been used to treat non-cardiogenic indications in non-pregnant individuals and the pediatric population. In pregnancy, labetalol is the mainstay treatment for hypertension and other cardiovascular indications. However, contraindications to certain sub-types of beta-blockers include bradycardia, heart failure, obstructive lung diseases, and hemodynamic instability. There is conflicting evidence of the adverse effects on fetal and neonatal health due to a scarce safety and efficacy profile, and further studies are necessary to understand the pharmacokinetics of the different classes of beta-blockers in pregnancy and fetal health. Understanding the hemodynamic changes during the stages of pregnancy is important to target a more beneficial therapy for both mother and fetus as well as better neonatal outcomes. Beta-blocker use in the pediatric population is less documented in studies but does have the potential to treat various cardiogenic and non-cardiogenic conditions. Future comprehensive studies would further benefit the direction of beta-blocker treatment during pregnancy in neonates and pediatrics.

Radiotherapy-associated sensorineural hearing loss in pediatric oncology patients.

During the radiotherapeutic treatment of pediatric oncology patients, they would be at a latent risk of developing ionizing radiation-induced ototoxicity when the cochlea or auditory nerve is located within the radiation field. Sensorineural hearing loss (SNHL) is an irreversible late complication of radiotherapy, and its incidence depends on various factors such as the patient's hearing sensitivity, total radiation dose to the cochlea, radiotherapy fractionation regimen, age and chemoradiation. Importantly, this complication exhibits serious challenges to adult survivors of childhood cancer, as it has been linked to impairments in academic achievement, psychosocial development, independent living skills, and employment in the survivor population. Therefore, early detection and proper management can alleviate academic, speech, language, social, and psychological morbidity arising from hearing deficits. In the present review, we have addressed issues such as underlying mechanisms of radiation-induced SNHL, audiometric findings of pediatric cancer patients treated with radiotherapy, and management and protection measures against radiation-induced ototoxicity.

Pharmacotherapeutic Potential of Natural Products to Target the SARS-CoV-2 PLpro Using Molecular Screening and Simulation Approaches.

Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development. To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120-140, 160-180, and 205-215. The 120-140 and 160-180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be - 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was - 35.58 ± 0.14 kcal/mol, for the NPC474594-PLpro, the TBE was - 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be - 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes.