Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

Nano-engineered vitamins as a potential epigenetic modifier against environmental air pollutants.

Air pollution has emerged as a serious threat to human health due to close association with spectrum of chronic ailments including cardiovascular disorders, respiratory diseases, nervous system dysfunctions, diabetes and cancer. Exposure to air-borne pollutants along with poor eating behaviours and inferior dietary quality irreversibly impacts epigenomic landscape, leading to aberrant transcriptional control of gene expression which is central to patho-physiology of non-communicable diseases. It is assumed that nutriepigenomic interventions such as vitamins can control such adverse effects through their immediate action on mitochondrial epigenomic-axis. Importantly, the exhaustive clinical utility of vitamins-interceded epigenetic synchronization is not well characterized. Therefore, improving the current limitations linked to stability and bioavailability issues in vitamin formulations is highly warranted. The present review not only sums up the available data on the role of vitamins as potential epigenetic modifiers but also discusses the importance of nano-engineered vitamins as potential epidrugs for dietary and pharmacological intervention to mitigate the long-term effects of air pollution toxicity.

Graphene Quantum-Dot-Based Nanophotonic Approach for Targeted Detection of Long Noncoding RNAs in Circulation.

Recent progress in the field of nanophotonics has opened up novel avenues for developing nanomaterial-based biosensing systems, which can detect various disease-specific biomarkers, including long noncoding RNAs (lncRNAs) known to circulate in biological fluids. Herein, we designed and developed a nanophotonic approach for rapid and specific capture of lncRNAs using oligonucleotide-conjugated graphene quantum-dot-nanoconjugates. The method offers accurate identification of the target lncRNAs with high selectivity, despite the presence of other molecules in the given sample. The observations also pointed toward the high feasibility and simplicity of the method in the selective determination of lncRNAs. Overall, the approach has the potential of assessing lncRNA expression as a function of disease initiation and progression.

Prenatal exposure to environmental pro-oxidants induces mitochondria-mediated epigenetic changes: a cross-sectional pilot study.

Mitochondria play a central role in maintaining cellular and metabolic homeostasis during vital development cycles of foetal growth. Optimal mitochondrial functions are important not only to sustain adequate energy production but also for regulated epigenetic programming. However, these organelles are subtle targets of environmental exposures, and any perturbance in the defined mitochondrial machinery during the developmental stage can lead to the re-programming of the foetal epigenetic landscape. As these modifications can be transferred to subsequent generations, we herein performed a cross-sectional study to have an in-depth understanding of this intricate phenomenon. The study was conducted with two arms: whereas the first group consisted of in utero pro-oxidant exposed individuals and the second group included controls. Our results showed higher levels of oxidative mtDNA damage and associated integrated stress response among the exposed individuals. These disturbances were found to be closely related to the observed discrepancies in mitochondrial biogenesis. The exposed group showed mtDNA hypermethylation and changes in allied mitochondrial functioning. Altered expression of mitomiRs and their respective target genes in the exposed group indicated the possibilities of a disturbed mitochondrial-nuclear cross talk. This was further confirmed by the modified activity of the mitochondrial stress regulators and pro-inflammatory mediators among the exposed group. Importantly, the disturbed DNMT functioning, hypermethylation of nuclear DNA, and higher degree of post-translational histone modifications established the existence of aberrant epigenetic modifications in the exposed individuals. Overall, our results demonstrate the first molecular insights of in utero pro-oxidant exposure associated changes in the mitochondrial-epigenetic axis. Although, our study might not cement an exposure-response relationship for any particular environmental pro-oxidant, but suffice to establish a dogma of mito-epigenetic reprogramming at intrauterine milieu with chronic illness, a hitherto unreported interaction.

Surface-enhanced Raman scattering biosensors for detection of oncomiRs in breast cancer.

Surface-enhanced Raman scattering (SERS) has emerged as one of the most promising platforms for various biosensing applications. These sensing systems encompass the advantages of specificity, ultra-high sensitivity, stability, low cost, repeatability, and easy-to-use methods. Moreover, their ability to offer a molecular fingerprint and identify the target analyte at low levels make SERS a promising technique for detecting circulating cancer biomarkers with greater sensitivity and reliability. Among the various circulating biomolecules, oncomiRs are emerging as prominent biomarkers for the early screening of breast cancers (BCs). In this review, we provide a comprehensive understanding of different SERS-based biosensors and their application to identify BC-specific oncomiRs. We also discuss different SERS-based sensing strategies, nano-analytical frameworks, and challenges to be addressed for effective clinical translation.