Insight Study of Trace Elements in PM2.5 During Nine Years in Delhi, India: Seasonal Variation, Source Apportionment, and Health Risks Assessment.

This study investigated the concentrations, seasonal variations, sources, and human health risks associated with exposure to heavy elements (As, Al, Pb, Cr, Mn, Cu, Zn, and Ni) of PM2.5 at an urban location of Delhi (28° 38' N, 77° 10' E; 218 m amsl), India, from January 2013 to December 2021. The average mass concentration of PM2.5 throughout the study period was estimated as 127 ± 77 µg m-3, which is exceeding the National Ambient Air Quality Standards (NAAQS) limit (annual: 40 µg m-3; 24 h: 60 µg m-3). The seasonal mass concentrations of PM2.5 exhibited at the order of post-monsoon (192 ± 110 µgm-3) > winter (158 ± 70 µgm-3) > summer (92 ± 44 µgm-3) and > monsoon (67 ± 32 µgm-3). The heavy elements, Al (1.19 µg m-3), Zn (0.49 µg m-3), Pb (0.43 µg m-3), Cr (0.21 µg m-3), Cu (0.21 µg m-3), Mn (0.07 µg m-3), and Ni (0.14 µg m-3) exhibited varying concentrations in PM2.5, with the highest levels observed in the post-monsoon season, followed by winter, summer, and monsoon seasons. Six primary sources throughout the study period, contributing to PM2.5 were identified by positive matrix factorization (PMF), such as dust (paved/crustal/soil dust: 29.9%), vehicular emissions (17.2%), biomass burning (15.4%), combustion (14%), industrial emissions (14.2%), and Br-rich sources (9.2%). Health risk assessments, including hazard quotient (HQ), hazard index (HI), and carcinogenic risk (CR), were computed based on heavy elements concentrations in PM2.5. Elevated HQ values for Cr and Mn linked with adverse health impacts in both adults and children. High carcinogenic risk values were observed for Cr in both adults and children during the winter and post-monsoon seasons, as well as in adults during the summer and monsoon seasons. The combined HI value exceeding one suggests appreciable non-carcinogenic risks associated with the examined elements. The findings of this study provide valuable insights into the behaviour and risk mitigation of heavy elements in PM2.5, contributing to the understanding of air quality and public health in the urban environment of Delhi.

Aquaporins Display a Diversity in their Substrates.

Aquaporins constitute a family of transmembrane proteins that function to transport water and other small solutes across the cell membrane. Aquaporins family members are found in diverse life forms. Aquaporins share the common structural fold consisting of six transmembrane alpha helices with a central water-transporting channel. Four such monomers assemble together to form tetramers as their biological unit. Initially, aquaporins were discovered as water-transporting channels, but several studies supported their involvement in mediating the facilitated diffusion of different solutes. The so-called water channel is able to transport a variety of substrates ranging from a neutral molecule to a charged molecule or a small molecule to a bulky molecule or even a gas molecule. This article gives an overview of a diverse range of substrates conducted by aquaporin family members. Prime focus is on human aquaporins where aquaporins show a wide tissue distribution and substrate specificity leading to various physiological functions. This review also highlights the structural mechanisms leading to the transport of water and glycerol. More research is needed to understand how one common fold enables the aquaporins to transport an array of solutes.

ARL6IP5 Ameliorates α-Synuclein Burden by Inducing Autophagy via Preventing Ubiquitination and Degradation of ATG12.

Recent advanced studies in neurodegenerative diseases have revealed several links connecting autophagy and neurodegeneration. Autophagy is the major cellular degradation process for the removal of toxic protein aggregates responsible for neurodegenerative diseases. More than 30 autophagy-related proteins have been identified as directly participating in the autophagy process. Proteins regulating the process of autophagy are much more numerous and unknown. To address this, in our present study, we identified a novel regulator (ARL6IP5) of neuronal autophagy and showed that the level of ARL6IP5 decreases in the brain with age and in Parkinson's disease in mice and humans. Moreover, a cellular model of PD (Wild type and A53T mutant α-synuclein overexpression) has also shown decreased levels of ARL6IP5. ARL6IP5 overexpression reduces α-synuclein aggregate burden and improves cell survival in an A53T model of Parkinson's disease. Interestingly, detailed mechanistic studies revealed that ARL6IP5 is an autophagy inducer. ARL6IP5 enhances Rab1-dependent autophagosome initiation and elongation by stabilizing free ATG12. We report for the first time that α-synuclein downregulates ARL6IP5 to inhibit autophagy-dependent clearance of toxic aggregates that exacerbate neurodegeneration.

The non-canonical nuclear functions of key players of the PI3K-AKT-MTOR pathway.

The PI3K-AKT-MTOR signal transduction pathway is one of the essential signalling cascades within the cell due to its involvement in many vital functions. The pathway initiates with the recruitment of phosphatidylinositol-3 kinases (PI3Ks) onto the plasma membrane, generating phosphatidylinositol-3,4,5-triphosphate [PtdIns(3,4,5)P3 ] and subsequently activating AKT. Being the central node of the PI3K network, AKT activates the mechanistic target of rapamycin kinase complex 1 (MTORC1) via Tuberous sclerosis complex 2 inhibition in the cytoplasm. Although the cytoplasmic role of the pathway has been widely explored for decades, we now know that most of the effector molecules of the PI3K axis diverge from the canonical route and translocate to other cell organelles including the nucleus. The presence of phosphoinositides (PtdIns) inside the nucleus itself indicates the existence of a nuclear PI3K signalling. The nuclear localization of these signaling components is evident in regulating many nuclear processes like DNA replication, transcription, DNA repair, maintenance of genomic integrity, chromatin architecture, and cell cycle control. Here, our review intends to present a comprehensive overview of the nuclear functions of the PI3K-AKT-MTOR signaling biomolecules.

Synthetic Tunability and Biophysical Basis for Fabricating Highly Fluorescent and Stable DNA Copper Nanoclusters.

The real motivation in the present work is to tune the synthesis variables that can result in a highly fluorescent and stable DNA copper nanocluster (CuNC) and also to understand the intricate mechanism behind this process. Here, carefully optimized concentrations of various reactants enabled the creation of a DNA-encapsulated CuNC for AT-DNA, displaying a size of <1.0 nm as confirmed by transmission electron microscopy and dynamic light scattering. The extremely small size of the AT-DNACuNC supports the discrete electronic transitions, also characterized by an exceptionally strong negative circular dichroism (CD) band around 350 nm, whose intensity is well correlated with the observed strong fluorescence emission intensity. This remarkably strong CD can open new applications in the detection and quantification of a specific DNACuNC. Further, time-dependent fluorescence analysis suggested stronger photostabilization of these DNACuNCs. The simulation study, based on Cu ion distribution, explained how AT-DNA is a better candidate for NC formation than GC-DNA. In conclusion, the better-tuned synthesis procedure has resulted in a highly compact, well-defined three-dimensional conformation that promotes a more favorable microenvironment to sequester a DNA-based CuNC with high brightness and outstanding photostability.

Development of novel anti-malarial from structurally diverse library of molecules, targeting plant-like CDPK1, a multistage growth regulator of P. falciparum.

Upon Plasmodium falciparum merozoites exposure to low [K+] environment in blood plasma, there is escalation of cytosolic [Ca2+] which activates Ca2+-Dependent Protein Kinase 1 (CDPK1), a signaling hub of intra-erythrocytic proliferative stages of parasite. Given its high abundance and multidimensional attributes in parasite life-cycle, this is a lucrative target for designing antimalarials. Towards this, we have virtually screened MyriaScreenII diversity collection of 10,000 drug-like molecules, which resulted in 18 compounds complementing ATP-binding pocket of CDPK1. In vitro screening for toxicity in mammalian cells revealed that these compounds are non-toxic in nature. Furthermore, SPR analysis demonstrated differential binding affinity of these compounds towards recombinantly purified CDPK1 protein. Selection of lead compound 1 was performed by evaluating their inhibitory effects on phosphorylation and ATP binding activities of CDPK1. Furthermore, in vitro biophysical evaluations by ITC and FS revealed that binding of compound 1 is driven by formation of energetically favorable non-covalent interactions, with different binding constants in presence and absence of Ca2+, and TSA authenticated stability of compound 1 bound CDPK1 complex. Finally, compound 1 strongly inhibited intra-erythrocytic growth of P. falciparum in vitro. Conceivably, we propose a novel CDPK1-selective inhibitor, step towards developing pan-CDPK kinase inhibitors, prerequisite for cross-stage anti-malarial protection.

Molecular dynamics simulations and biochemical characterization of Pf14-3-3 and PfCDPK1 interaction towards its role in growth of human malaria parasite.

Scaffold proteins play pivotal role as modulators of cellular processes by operating as multipurpose conformation clamps. 14-3-3 proteins are gold-standard scaffold modules that recognize phosphoSer/Thr (pS/pT) containing conserved motifs, and confer conformational changes leading to modulation of functional parameters of their target proteins. Modulation in functional activity of kinases has been attributed to their interaction with 14-3-3 proteins. Herein, we have annotated and characterized PF3D7_0818200 as 14-3-3 isoform I in Plasmodium falciparum 3D7, and its interaction with one of the key kinases of the parasite, Calcium-Dependent Protein Kinase 1 (CDPK1) by performing various analytical biochemistry and biophysical assays. Molecular dynamics simulation studies indicated that CDPK1 polypeptide sequence (61KLGpS64) behaves as canonical Mode I-type (RXXpS/pT) consensus 14-3-3 binding motif, mediating the interaction. The 14-3-3I/CDPK1 interaction was validated in vitro with ELISA and SPR, which confirmed that the interaction is phosphorylation dependent, with binding affinity constant of 670 ± 3.6 nM. The interaction of 14-3-3I with CDPK1 was validated with well characterized optimal 14-3-3 recognition motifs: Mode I-type ARSHpSYPA and Mode II-type RLYHpSLPA, by simulation studies and ITC. This interaction was found to marginally enhance CDPK1 functional activity. Furthermore, interaction antagonizing peptidomimetics showed growth inhibitory impact on the parasite indicating crucial physiological role of 14-3-3/CDPK1 interaction. Overall, this study characterizes 14-3-3I as a scaffold protein in the malaria parasite and unveils CDPK1 as its previously unidentified target. This sets a precedent for the rational design of 14-3-3 based PPI inhibitors by utilizing 14-3-3 recognition motif peptides, as a potential antimalarial strategy.

Varietal influence on phenolic constituents and nutritive characteristics of pomace obtained from apples grown in western Himalayas.

Apple fruit processing is not variety specific in India, which affect the overall quality of the final processed product. The present study was aimed at elucidation of the nutritive value, phenolic content, antioxidant activity and bioactive phenolic constituents of five widely used apple varieties (Royal Delicious, Red Delicious, Golden Delicious, Red Chief and Red Gold) of western Himalayas. The pomace obtained from different varieties was evaluated to assess the fruit quality. Royal Delicious pomace had significantly high (p < 0.05) total dietary fibre content (42.63 ± 1.26%) together with soluble (8.25 ± 0.95%) and insoluble fibre (32.90 ± 0.89%), as compared to other apple varieties. The pomace samples were extracted with 70% aqueous methanol to obtain polyphenol enriched extracts. The results of Folin-Ciocalteau assay showed that hydroalcoholic extract of Royal Delicious pomace exhibit higher phenolic content as compared to other varieties and ranged between 2.19 ± 0.09 and 4.59 ± 0.47 mg GAE/g. Royal Delicious pomace also possess higher antioxidant capacity i.e. 3.35 ± 0.10 mg/g, 2.71 ± 0.10 mg/g and 4.67 ± 0.03 mg/g as measured by DPPH, ABTS free radical scavenging assay and FRAP reducing assay, respectively. The higher phenolic content in Royal Delicious pomace was also confirmed by RP-HPLC-DAD analysis. Results of HPLC analysis revealed the presence of phloridzin (487.07 ± 0.04 µg/g), quercetin (241.18 ± 0.03 µg/g), quercitrin (178.34 ± 0.02 µg/g) and quercetin-3-glucoside (195.21 ± 0.05 µg/g) as major constituents. Present results indicate that Royal Delicious variety is rich in dietary fibre and phenolic compounds that might be used by the food sector as a source of bioactive health promoting constituents/dietary supplements.

A De novo Peptide from a High Throughput Peptide Library Blocks Myosin A -MTIP Complex Formation in Plasmodium falciparum.

Apicomplexan parasites, through their motor machinery, produce the required propulsive force critical for host cell-entry. The conserved components of this so-called glideosome machinery are myosin A and myosin A Tail Interacting Protein (MTIP). MTIP tethers myosin A to the inner membrane complex of the parasite through 20 amino acid-long C-terminal end of myosin A that makes direct contacts with MTIP, allowing the invasion of Plasmodium falciparum in erythrocytes. Here, we discovered through screening a peptide library, a de-novo peptide ZA1 that binds the myosin A tail domain. We demonstrated that ZA1 bound strongly to myosin A tail and was able to disrupt the native myosin A tail MTIP complex both in vitro and in vivo. We then showed that a shortened peptide derived from ZA1, named ZA1S, was able to bind myosin A and block parasite invasion. Overall, our study identified a novel anti-malarial peptide that could be used in combination with other antimalarials for blocking the invasion of Plasmodium falciparum.

Hard and soft-tissue evaluation of bar-clip, ball-socket, and kerator attachments in mandibular implant overdenture treatment: An in vivo study.

AIM: The aim of this in vivo study was to evaluate and compare the soft and hard tissue changes in implant supported mandibular overdenture with three different attachment system. SETTINGS AND DESIGN: In vivo - observation study. MATERIALS AND METHODS: After evaluation of prosthetic space, fifteen edentulous subjects received two implants in the inter-foramina region of the mandible and were divided into 3 groups with 5 subjects each, delayed loading protocol was followed in all the patients. The crestal bone loss, modified sulcular bleeding index, plaque index values were evaluate with the attachments at baseline and after 6 months was measured in a standardised way. STATISTICAL ANALYSIS USED: Oneway ANOVA test and post hoc Bonferroni multiple test. RESULTS: At the end of six months modified sulcular bleeding index and plaque index values was higher in Group 2 (bar and clip attachment) as compared to Group 1 (ball and socket attachment) and Group 3 (Kerator attachment) and crestal bone loss was equal in groups 1, 2 and 3. Analysis of variance with repeated measures showed significant differences in modified sulcular bleeding index and plaque index among the three attachment types. CONCLUSION: (1) Group 2 (bar-and-clip attachment) exhibited higher Modified Sulcular Bleeding Index and Plaque Index values than Group 1 (ball-and-socket attachment) and Group 3 (kerator attachment). (2) Crestal bone loss was equal in Group 1 (ball-and-socket attachment), Group 2 (bar-and-clip attachment), and Group 3 (kerator attachment).

Modulation of prion polymerization and toxicity by rationally designed peptidomimetics.

Misfolding and aggregation of cellular prion protein is associated with a large array of neurological disorders commonly called the transmissible spongiform encephalopathies. Designing inhibitors against prions has remained a daunting task owing to limited information about mechanism(s) of their pathogenic self-assembly. Here, we explore the anti-prion properties of a combinatorial library of bispidine-based peptidomimetics (BPMs) that conjugate amino acids with hydrophobic and aromatic side chains. Keeping the bispidine unit unaltered, a series of structurally diverse BPMs were synthesized and tested for their prion-modulating properties. Administration of Leu- and Trp-BPMs delayed and completely inhibited the amyloidogenic conversion of human prion protein (HuPrP), respectively. We found that each BPM induced the HuPrP to form unique oligomeric nanostructures differing in their biophysical properties, cellular toxicities and response to conformation-specific antibodies. While Leu-BPMs were found to stabilize the oligomers, Trp-BPMs effected transient oligomerization, resulting in the formation of non-toxic, non-fibrillar aggregates. Yet another aromatic residue, Phe, however, accelerated the aggregation process in HuPrP. Molecular insights obtained through MD (molecular dynamics) simulations suggested that each BPM differently engages a conserved Tyr 169 residue at the α2-ß2 loop of HuPrP and affects the stability of α2 and α3 helices. Our results demonstrate that this new class of molecules having chemical scaffolds conjugating hydrophobic/aromatic residues could effectively modulate prion aggregation and toxicity.

Infection control knowledge and practice: A cross-sectional survey on dental laboratories in dental institutes of North India.

AIM AND OBJECTIVES: The aim of the study was to assess the knowledge of dental laboratory technicians regarding infection control and modes of infection control employed by them. SETTINGS AND DESIGN: A self-assessment questionnaire-based survey was carried out among dental technicians to assess the knowledge and practice of infection control in dental laboratories. MATERIALS AND METHODS: Survey instrument containing 16 questions were randomly distributed to 70 dental colleges of North India regarding knowledge of infection control methods and infection control practised in laboratories. Data were collected and analyzed. RESULTS: The response showed that 30.76% of dental technicians receive 30-50 or more than 50 impressions in a week. About 96.15% of the technicians used a plastic bag to carry impressions. Twenty-five percent of the dental technicians were aware of infection control protocol. Fifty-five percent of the technicians received impressions while wearing gloves and 61.53% of the institutes had a separate receiving area. Nearly 71.15% of the technicians communicate with the doctor regarding the disinfection of impression received in the laboratory. Almost 30.76% of the dental technicians disinfect all the impressions and 67.30% technicians use immersion for disinfection of impressions. Only 38.46% responded that they immerse impressions for 10 min for disinfection. About 73.07% use gloves, 90.38% use mouth masks, 57.69% wear eye shields, and 88.46% wear aprons while working. Nearly 78.84% of the technicians received vaccination against hepatitis B virus. Almost 69.23% of the technicians change pumice slurry after regular intervals, and 75% do not add any disinfectant. Nearly 59.61% of technicians disinfect the prostheses before sending it to the clinic, and 42.30% disinfect them by immersion technique. About disposal of waste, 80.76% said that they dispose the waste properly. CONCLUSION: To summarize, most of the technicians were not aware of basic infection control protocols.

SOCS3 induces neurite differentiation and promotes neuronal cell survival.

Cytokines and growth factors play an important role in neuronal survival as well as cell death. The family of suppressors of cytokine signalling (SOCS) proteins, which includes SOCS1-7 and cytokine-induced suppressor (CIS), has been shown to act as negative regulators of cytokine-induced signalling. In this report, we highlight the role of SOCS3 in regulating neuronal differentiation and survival. We observed increased SOCS3 expression upon differentiation of PC12 cells as well as neural stem cells. SOCS3 overexpression upregulated differentiation of both neural stem cells and PC12 cells even in the absence of NGF, as evidenced by enhanced neurite outgrowth and upregulation of GAP43, marker associated with neurite outgrowth. siRNA-mediated silencing of SOCS3 confirmed the potential role of SOCS3 in neuritogenesis. We observed that, SOCS3-induced neurite differentiation was mediated via the PI3 kinase pathway. Another interesting observation was that SOCS3 overexpression promoted neuronal cell survival under H2 O2 -mediated stress indicating its fundamental role in cell survival. In conclusion, our results indicate that SOCS3 promotes differentiation and survival of neural cells and could be potentially useful in future therapy for treatment of neurodegenerative disorders. © 2016 IUBMB Life, 68(6):468-476, 2016.

Evolutionary dynamics of the plastid inverted repeat: the effects of expansion, contraction, and loss on substitution rates.

Rates of nucleotide substitution were previously shown to be several times slower in the plastid inverted repeat (IR) compared with single-copy (SC) regions, suggesting that the IR provides enhanced copy-correction activity. To examine the generality of this synonymous rate dependence on the IR, we compared plastomes from 69 pairs of closely related species representing 52 families of angiosperms, gymnosperms, and ferns. We explored the breadth of IR boundary shifts in land plants and demonstrate that synonymous substitution rates are, on average, 3.7 times slower in IR genes than in SC genes. In addition, genes moved from the SC into the IR exhibit lower synonymous rates consistent with other IR genes, while genes moved from the IR into the SC exhibit higher rates consistent with other SC genes. Surprisingly, however, several plastid genes from Pelargonium, Plantago, and Silene have highly accelerated synonymous rates despite their IR localization. Together, these results provide strong evidence that the duplicative nature of the IR reduces the substitution rate within this region. The anomalously fast-evolving genes in Pelargonium, Plantago, and Silene indicate localized hypermutation, potentially induced by a higher level of error-prone double-strand break repair in these regions, which generates substitutional rate variation.

Efficacy of Bacillus Calmette-Guérin in Cancer Prevention and Its Putative Mechanisms.

Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis. Although it was developed as a prophylactic vaccine against tuberculosis (TB), researchers have also evaluated it for preventing cancer development or progression. These studies were inspired by the available data regarding the protective effects of microbial infection against cancers and an inverse relationship between TB and cancer mortality. Initial studies demonstrated the efficacy of BCG in preventing leukemia, melanoma and a few other cancers. However, mixed results were observed in later studies. Importantly, these studies have led to the successful use of BCG in the tertiary prevention of non-muscle invasive bladder cancer, wherein BCG therapy has been found to be more effective than chemotherapy. Moreover, in a recently published 60-year follow-up study, childhood BCG vaccination has been found to significantly prevent lung cancer development. In the present manuscript, we reviewed the studies evaluating the efficacy of BCG in cancer prevention and discussed its putative mechanisms. Also, we sought to explain the mixed results of BCG efficacy in preventing different cancers.

Role of Phytoconstituents in Cancer Treatment: A Review.

Over the years, natural compounds have become a significant advancement in cancer treatment, primarily due to their effectiveness, safety, bio-functionality, and wide range of molecular structures. They are now increasingly preferred in drug discovery due to these attributes. These compounds, whether occurring naturally or with synthetic modifications, find applications in various fields like biology, medicine, and engineering. While chemotherapy has been a successful method for treating cancer, it comes with systemic toxicity. To address this issue, researchers and medical practitioners are exploring the concept of combinational chemotherapy. This approach aims to reduce toxicity by using a mix of natural substances and their derivatives in clinical trials and prescription medications. Among the most extensively studied natural anticancer compounds are quercetin, curcumin, vincristine, and vinblastine. These compounds play crucial roles as immunotherapeutics and chemosensitizers, both as standalone treatments and in combination therapies with specific mechanisms. This review article provides a concise overview of the functions, potentials, and combinations of natural anticancer compounds in cancer treatment, along with their mechanisms of action and clinical applications.

Comparative evaluation of resin-based sealers and bioceramic sealers for postoperative pain after endodontic treatment: A systematic review.

The systematic review aimed to compare and evaluate the effect of resin-based sealers and bioceramic sealers on postoperative pain after endodontic treatment. Two reviewers independently conducted electronic search in PubMed, the Web of Science, ScienceDirect, the Wiley Online Library, SpringerLink, Google Scholar, and the Cochrane Library, employing a complete dual-review process to ensure the inclusion of all relevant studies in the review. The search was carried out until November 2021. After selecting eligible studies, the risk of bias assessment was carried out using the revised Cochrane risk-ofbias tool for randomized trials (RoB 2). A total of 1,931 studies were identified from the electronic search, and finally 10 studies were included after full-text assessment. In all our included studies, the visual analog scale (VAS) was used for recording pain scores. Most of the studies recorded pain intensity starting from 6 h to 7 days. The results showed that there was no significant difference between resin-based sealers and bioceramic sealers in terms of incidence or intensity of postoperative pain at any point in time.

Phytochemical investigation and characterisation of methanolic extract of Glycine max seeds using LCMS/MS and in silico studies for wound healing activity.

Soybean is scientifically known as Glycine max. It belongs to the Fabaceae family. It consists of a lot of bioactive phytochemicals like saponin, phenolic acid, flavonoid, sphingolipids and phytosterols. It also owns excellent immune-active effects in the physiological system. Soy and its phytochemicals have been found to have pharmacological properties that include anticancer, antioxidant, anti-hypercholesterolaemic, anti-diabetic, oestrogenic, anti-hyperlipidaemic, anti-inflammatory, anti-obesity, anti-hypertensive, anti-mutagenic, immunomodulatory, anti-osteoporotic, antiviral, hepatoprotective, antimicrobial, goitrogenic anti-skin ageing, wound healing, neuroprotective and anti-photoageing activities. Present study has been designed to set standard pharmacognostical extraction method, complexation of compounds, qualitative evaluation through phytochemical screening, identification by TLC, physicochemical properties, solubility profile, total phenolic, flavonoid content as well as analytical evaluation or characterisation like UV and FT-IR of methanolic extract of G. max. The final observations like physicochemical properties such as total ash value, LOD and pH were recorded. Phytochemical screenings show the presence of flavonoid, alkaloid, saponin, carbohydrate, tannins, protein, gums and mucilage, fixed oils and fats. The results were found significant. Further in silico studies proved creatinine and euparin to be potent wound healing agents.

FIGO 2023 endometrial staging: a leap of faith into the new "prognostic based' rather than "anatomical based" staging-too fast too furious??

BACKGROUND: In 2023 FIGO revised the endometrial cancer staging system after 13 years. There is a lacuna of data regarding the performance and practicality of the revised 2023 FIGO staging schema for endometrial cancer from Low Middle-Income Countries (LMIC). OBJECTIVE: To estimate the shift of stage and adjuvant management of endometrial cancer based on the FIGO 2023 system compared to the FIGO 2009 system and assess the predictive potential of the FIGO 2023 system. MATERIAL AND METHODS: A retrospective study was conducted from 1st January 2017 to 31st December 2022. All patients with endometrial cancer were staged according to the FIGO 2023 and FIGO 2009 staging system. Follow-up of patients was done to determine recurrence. RESULTS: A total of 152 patients were included. Aggressive histology was seen in 66 (45%) patients. Eighteen (11%) had subserosal involvement. Substantial LVSI was noted in 23 (15%) of patients. Twenty-four (47%) patients of FIGO 2009 Stage IA and 26 patients (63%) of FIGO 2009 Stage IB were upstaged. Eleven (50%) patients of FIGO 2009 Stage IIIA were down staged to IA3. Overall 23 patients (15%) had a shift of stage. Fifteen out of 152 patients (15%) would have had a possible risk stratification change which would imply 23 patients (15%) would have needed a more radical treatment. Molecular classification was done in 32 patients; however, only 2 patients could afford POLE testing. Kaplan-Meier curves showed significant PFS differences in FIGO 2009 Stage IB and Stage IIIA when restaged according to the FIGO 2023 system. CONCLUSION: The FIGO 2023 endometrial staging is a more robust prognosticator; however, the practicality of molecular classification in LMICs is still a distant dream.