Congenital rubella syndrome surveillance in India, 2016-21: Analysis of five years surveillance data.

Background: In India, facility-based surveillance for congenital rubella syndrome (CRS) was initiated in 2016 to estimate the burden and monitor the progress made in rubella control. We analyzed the surveillance data for 2016-2021 from 14 sentinel sites to describe the epidemiology of CRS. Method: We analyzed the surveillance data to describe the distribution of suspected and laboratory confirmed CRS patients by time, place and person characteristics. We compared clinical signs of laboratory confirmed CRS and discarded case-patients to find independent predictors of CRS using logistic regression analysis and developed a risk prediction model. Results: During 2016-21, surveillance sites enrolled 3940 suspected CRS case-patients (Age 3.5 months, SD: 3.5). About one-fifth (n = 813, 20.6%) were enrolled during newborn examination. Of the suspected CRS patients, 493 (12.5%) had laboratory evidence of rubella infection. The proportion of laboratory confirmed CRS cases declined from 26% in 2017 to 8.7% in 2021. Laboratory confirmed patients had higher odds of having hearing impairment (Odds ratio [OR] = 9.5, 95% confidence interval [CI]: 5.6-16.2), cataract (OR = 7.8, 95% CI: 5.4-11.2), pigmentary retinopathy (OR = 6.7, 95 CI: 3.3-13.6), structural heart defect with hearing impairment (OR = 3.8, 95% CI: 1.2-12.2) and glaucoma (OR = 3.1, 95% CI: 1.2-8.1). Nomogram, along with a web version, was developed. Conclusions: Rubella continues to be a significant public health issue in India. The declining trend of test positivity among suspected CRS case-patients needs to be monitored through continued surveillance in these sentinel sites.

Tyrosine-Generated Nanostructures Initiate Amyloid Cross-Seeding in Proteins Leading to a Lethal Aggregation Trap.

Here, we show that aromatic amino acid tyrosine, under a physiologically mimicking condition, readily forms amyloid-like entities that can effectively drive aggregation of different globular proteins and aromatic residues. Tyrosine self-assembly resulted in the formation of cross-ß rich regular fibrils as well as spheroidal oligomers. Computational data suggest intermolecular interaction between specifically oriented tyrosine molecules mediated through π-π stacking and H-bonding interactions, mimicking a cross-ß-like architecture. Both individual protein samples and mixed protein samples underwent aggregation in the presence of tyrosine fibrils, confirming the occurrence of amyloid cross-seeding. The surface of the tyrosine's amyloid like entities was predicted to trap native protein structures, preferably through hydrophobic and electrostatic interactions initiating an aggregation event. Because tyrosine is a precursor to vital neuromodulators, the inherent cross-seeding potential of the tyrosine fibrils may have direct relevance to amyloid-linked pathologies.

Intrinsic property of phenylalanine to trigger protein aggregation and hemolysis has a direct relevance to phenylketonuria.

Excess accumulation of phenylalanine is the characteristic of untreated Phenylketonuria (PKU), a well-known genetic abnormality, which triggers several neurological, physical and developmental severities. However, the fundamental mechanism behind the origin of such diverse health problems, particularly the issue of how they are related to the build-up of phenylalanine molecules in the body, is largely unknown. Here, we show cross-seeding ability of phenylalanine fibrils that can effectively initiate an aggregation process in proteins under physiological conditions, converting native protein structures to ß-sheet assembly. The resultant fibrils were found to cause severe hemolysis, yielding a plethora of deformed erythrocytes that is highly relevant to phenylketonuria. Unique arrangement of zwitterionic phenylalanine molecules in their amyloid-like higher order entities is predicted to promote both hydrophobic and electrostatic interaction, sufficient enough to trap proteins and to preferentially interact with the membrane components of RBCs. Since the prevalence of hemolysis and amyloid related psychoneurological severities are mostly observed in PKU patients, we propose that the inherent property of phenylalanine fibrils to trigger hemolysis and to induce protein aggregation may have direct relevance to the disease mechanism of PKU.

Uniform, Polycrystalline, and Thermostable Piperine-Coated Gold Nanoparticles to Target Insulin Fibril Assembly.

Because the process of insulin fibril assembly is linked to a multitude of medical problems, finding effective and biocompatible inhibitors against such an aggregation process could be beneficial. Targeting the aggregation-prone residues of insulin may perhaps work as an effective strategy to prevent the onset of insulin fibril assembly. In this work, we have synthesized uniform sized, thermostable gold nanoparticles (AuNPspiperine) surface-functionalized with piperine to target amyloid-prone residues of insulin. We found that the process of both spontaneous and seed-induced amyloid formation of insulin was strongly inhibited in the presence of AuNPspiperine. Surface functionalization of piperine was found to be critical to its inhibition effect because no such effect was observed for free piperine as well as for uncoated control gold nanoparticles. Fluorescence quenching data revealed binding of AuNPspiperine with insulin's native structure which was further validated by docking studies that predicted viable H-bond and CH-π interactions between piperine and key aggregation-prone residues of insulin's B-chain. Our hemolysis assay studies further confirmed that these piperine coated nanoparticles were hemocompatible. Data obtained from both experimental and computational studies suggest that the retention of native structure of insulin and the ability of the piperine molecule to interact with the aggregation-prone residues of insulin are the key factors for the inhibition mechanism. The findings of this work may help in the development of nanoparticle-based formulations to prevent medical problems linked to insulin aggregation.