Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

Bibliometric analysis of orthopaedic related publications by Indian authors from the last decade

PurposeBibliometric studies have been established methods of analysing publications on a particular topic. These studies have been done on various orthopaedic topics and are increasing. The advantages of these studies have been highlighted in previous publications. Although some studies have been done on Indian publications from other specialties, those analysing Indian Orthopaedic Publications are lacking.MethodsWe performed a search in Scopus to look for all publications related to orthopaedics from India. Our search strategy in Scopus included ((TITLE-ABS-KEY(Orthopaedics OR Orthopaedics) AND AFFIL(India)) AND PUBYEAR > 2009 AND PUBYEAR < 2020) which resulted in 3270 articles on 02/11/2021. We analyzed the most publishing universities, city, state, specialty, authors, and anatomic location of these publications. We also mined the data to draw word clouds based on data obtained from the titles of articles, keywords and the affiliations of each of the articles published.ResultsTamil Nadu and New Delhi and their institutes appear to be the epicenter of publication activities in Orthopaedics in India. There has been a healthy trend of growth of articles in the orthopaedic specialty. Since there is a significant overlap of technology and engineering, it is not surprising to see engineering and technology institutes among the top 10 published institutes and even journals for the publications on orthopaedics.ConclusionThere has been a steady increase in the number of publications in the last decade. New Delhi and its Universities and Institutes appear to contribute the majority of citations and publications related to orthopaedics. Journal of Clinical Orthopaedics and Trauma was the most publishing journal for Indian authors on Orthopaedic related articles.     

Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl₂-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl₂ treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl₂, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl₂-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca²⁺-CaMKII-dependent Akt/mTOR pathway.     

Registries,Databases and Repositories for Developing Artificial Intelligence in Cancer Care

Modern artificial intelligence techniques have solved some previously intractable problems and produced impressive results in selected medical domains. One of their drawbacks is that they often need very large amounts of data. Pre-existing datasets in the form of national cancer registries, image/genetic depositories and clinical datasets already exist and have been used for research. In theory, the combination of healthcare Big Data with modern, data-hungry artificial intelligence techniques should offer significant opportunities for artificial intelligence development, but this has not yet happened. Here we discuss some of the structural reasons for this, barriers preventing artificial intelligence from making full use of existing datasets, and make suggestions as to enable progress. To do this, we use the framework of the 6Vs of Big Data and the FAIR criteria for data sharing and availability (Findability, Accessibility, Interoperability, and Reuse). We share our experience in navigating these barriers through The Brain Tumour Data Accelerator, a Brain Tumour Charity-supported initiative to integrate fragmented patient data into an enriched dataset. We conclude with some comments as to the limits of such approaches.     

Endocrine manifestations of chronic kidney disease and their evolving management: A systematic review

BackgroundChronic Kidney Disease (CKD) shows a wide range of renal abnormalities including the excretory, metabolic, endocrine, and homeostatic function of the kidney. The prognostic impact of the ‘endocrine manifestations’ which are often overlooked by clinicians cannot be overstated.Methods and objectivesA systematic review was attempted to provide a comprehensive overview of all endocrine abnormalities of CKD and their evolving principles of management, searching databases of PubMed, Embase, and Scopus and covering the literature between 2002 and 2022.ResultsThe endocrine derangements in CKD can be attributed to a myriad of pathologic processes, in particular decreased clearance, impaired endogenous hormone production, uremia-induced cellular dysfunction, and activation of systemic inflammatory pathways. The major disorders include anemia, hyperprolactinemia, insulin resistance, reproductive hormone deficiency, thyroid hormone deficiency, and serum FGF (Fibroblast Growth Factor) alteration. Long-term effects of CKD also include malnutrition and increased cardiovascular risk. The recent times have unveiled their detailed pathogenesis and have seen an evolution in the principles of management which necessitates a revision of current guidelines.ConclusionIncreased advertence regarding the pathology, impact, and management of these endocrine derangements can help in reducing morbidity as well as mortality in the CKD patients by allowing prompt individualized treatment. Moreover, with timely and appropriate intervention, a long-term reduction in complications, as well as an enhanced quality of life, can be achieved in patients with CKD.