183 results on '"Sekar R."'
Search Results
2. Prevalence of unnecessary kidney function exclusion criteria in urologic oncology clinical trials.
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Bank M, Krischak M, Skolarus T, Lewicki P, Sekar R, Herrel L, Barnes GD, Ghani K, Piatt G, Vince R, and Stensland K
- Abstract
Introduction: Clinical trials play a pivotal role in advancing treatments for people with cancer, but often struggle with low enrollment. Unnecessarily including kidney function eligibility criteria when a trial's interventions do not have any potential kidney effects may contribute to this problem by needlessly limiting the pool of eligible patients, adding complexity to the patient screening process, and raising issues of inequitable access to trials. For these reasons, we applied custom natural language processing to assess renal function eligibility criteria, and the appropriateness of these exclusions, within phase 3 urologic oncology trials., Methods: We accessed all phase 3 urologic oncology trials registered on ClinicalTrials.gov from 2007 to 2021. We used a custom natural language processing script to extract kidney function requirements (e.g., creatinine, GFR) from trial free-text records. For each trial, we manually coded whether any trial intervention affected renal function or was renally excreted. Additionally, we recorded the formula used to calculate GFR in each trial., Results: Of 850 trials, 299 (35%) listed kidney function eligibility restrictions, and 432 (51%) tested an intervention with possible renal effects. Of the 299 trials with kidney function exclusions, 124 (41%) tested interventions with no kidney effects., Conclusion: There is a major disconnect in urologic oncology clinical trials between renal function exclusions and potential harm to the kidneys from the tested interventions. Standardizing eligibility criteria and restricting enrollment based on renal function only when necessary has the potential to increase the success, access, and applicability of clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)
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- 2024
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3. Promising and challenging phytochemicals targeting LC3 mediated autophagy signaling in cancer therapy.
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Rajendran P, Renu K, Ali EM, Genena MAM, Veeraraghavan V, Sekar R, Sekar AK, Tejavat S, Barik P, and Abdallah BM
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- Humans, Animals, Oxidative Stress drug effects, Autophagy drug effects, Neoplasms drug therapy, Neoplasms metabolism, Neoplasms pathology, Signal Transduction drug effects, Phytochemicals pharmacology, Phytochemicals therapeutic use, Microtubule-Associated Proteins metabolism
- Abstract
Background: Phytochemicals possess a wide range of anti-tumor properties, including the modulation of autophagy and regulation of programmed cell death. Autophagy is a critical process in cellular homeostasis and its dysregulation is associated with several pathological conditions, such as cancer, neurodegenerative diseases, and diabetes. In cancer, autophagy plays a dual role by either promoting tumor growth or suppressing it, depending on the cellular context. During autophagy, autophagosomes engulf cytoplasmic components such as proteins and organelles. LC3-II (microtubule-associated protein 1 light chain 3-II) is an established marker of autophagosome formation, making it central to autophagy monitoring in mammals., Objective: To explore the regulatory role of phytochemicals in LC3-mediated autophagy and their potential therapeutic impact on cancer. The review emphasizes the involvement of autophagy in tumor promotion and suppression, particularly focusing on autophagy-related signaling pathways like oxidative stress through the NRF2 pathway, and its implications for genomic stability in cancer development., Methods: The review focuses on a comprehensive analysis of bioactive compounds including Curcumin, Celastrol, Resveratrol, Kaempferol, Naringenin, Carvacrol, Farnesol, and Piperine. Literature on these compounds was examined to assess their influence on autophagy, LC3 expression, and tumor-related signaling pathways. A systematic literature search was conducted across databases including PubMed, Scopus, and Web of Science from inception to 2023. Studies were selected from prominent databases, focusing on their roles in cancer diagnosis and therapeutic interventions, particularly in relation to LC3-mediated mechanisms., Results: Phytochemicals have been shown to modulate autophagy through the regulation of LC3-II levels and autophagic flux in cancer cells. The interaction between autophagy and other cellular pathways such as oxidative stress, inflammation, and epigenetic modulation highlights the complex role of autophagy in tumor biology. For instance, Curcumin and Resveratrol have been reported to either induce or inhibit autophagy depending on cancer type, influencing tumor progression and therapeutic responses., Conclusion: Targeting autophagy through LC3 modulation presents a promising strategy for cancer therapy. The dual role of autophagy in tumor suppression and promotion, however, necessitates careful consideration of the context in which autophagy is induced or inhibited. Future research should aim to delineate these context-specific roles and explore how phytochemicals can be optimized for therapeutic efficacy. Novel therapeutic strategies should focus on the use of bioactive compounds to fine-tune autophagy, thereby maximizing tumor suppression and inducing programmed cell death in cancer cells., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)
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- 2024
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4. The role of MicroRNAs in the diagnosis and treatment of oral premalignant disorders.
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Fathima JHS, Jayaraman S, Sekar R, and Syed NH
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- Humans, Biomarkers, Tumor, MicroRNAs, Precancerous Conditions genetics, Precancerous Conditions therapy, Precancerous Conditions diagnosis, Mouth Neoplasms diagnosis, Mouth Neoplasms genetics, Mouth Neoplasms therapy
- Abstract
Oral premalignant disorders (OPMDs) are a group of potentially malignant conditions that pose a significant health burden globally. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as crucial regulators of gene expression and have been implicated in various biological processes, including carcinogenesis. This review synthesizes existing knowledge to provide a comprehensive understanding of the molecular mechanisms underlying OPMDs and to highlight the potential of miRNAs as promising biomarkers and therapeutic targets. Additionally, this review seeks to explore the potential of miRNA-based diagnostic biomarkers for early detection of OPMDs in the current literature on miRNAs in OPMDs, examining their involvement in disease pathogenesis, diagnostic potential, and therapeutic implications. Dysregulated miRNAs can target genes involved in critical cellular processes, such as cell cycle regulation, apoptosis, and DNA repair, leading to disease progression. Notably, miR-21, miR-31, miR-135b, and miR-486-5p have shown promise as potential biomarkers for early detection of oral premalignant lesions. Furthermore, the paper discusses the therapeutic implications of miRNAs in OPMDs. Preclinical studies have demonstrated the efficacy of miRNA-targeted therapies, such as miRNA mimics and inhibitors, in suppressing the growth of oral premalignant lesions. Early-phase clinical trials have shown promising results, indicating the potential for personalized treatment approaches. The findings underscore the importance of understanding the molecular mechanisms underlying these disorders and provide insights for the development of improved diagnostic and therapeutic strategies. However, they pose certain limitations given their intrinsic variability in expression profiles, the need for optimized isolation and detection methods, and potential hurdles in transitioning from preclinical success to clinical applications. Thus, future clinical studies are warranted to fully exploit the potential of miRNAs in the management of OPMDs., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)
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- 2024
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5. Mixotrophic aerobic denitrification facilitated by denitrifying bacterial-fungal communities assisted with iron in micro-polluted water: Performance, metabolic activity, functional genes abundance, and community co-occurrence.
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Ma B, Chu M, Zhang H, Chen K, Li F, Liu X, Kosolapov DB, Zhi W, Chen Z, Yang J, Deng Y, Sekar R, Liu T, Liu X, and Huang T
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- Bioreactors, Nitrates metabolism, Aerobiosis, Water Purification methods, Denitrification, Iron metabolism, Iron chemistry, Water Pollutants, Chemical metabolism, Fungi metabolism, Fungi genetics, Bacteria genetics, Bacteria metabolism
- Abstract
Low-dosage nitrate pollutants can contribute to eutrophication in surface water bodies, such as lakes and reservoirs. This study employed assembled denitrifying bacterial-fungal communities as bio-denitrifiers, in combination with zero-valent iron (ZVI), to treat micro-polluted water. Immobilized bacterial-fungal mixed communities (IBFMC) reactors demonstrated their ability to reduce nitrate and organic carbon by over 43.2 % and 53.7 %, respectively. Compared to IBFMC reactors, IBFMC combined with ZVI (IBFMC@ZVI) reactors exhibited enhanced removal efficiencies for nitrate and organic carbon, reaching the highest of 31.55 % and 17.66 %, respectively. The presence of ZVI in the IBFMC@ZVI reactors stimulated various aspects of microbial activity, including the metabolic processes, electron transfer system activities, abundance of functional genes and enzymes, and diversity and richness of microbial communities. The contents of adenosine triphosphate and electron transfer system activities enhanced more than 5.6 and 1.43 folds in the IBFMC@ZVI reactors compared with IBFMC reactors. Furthermore, significant improvement of crucial genes and enzyme denitrification chains was observed in the IBFMC@ZVI reactors. Iron played a central role in enhancing microbial diversity and activity, and promoting the supply, and transfer of inorganic electron donors. This study presents an innovative approach for applying denitrifying bacterial-fungal communities combined with iron enhancing efficient denitrification in micro-polluted water., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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6. Letter to editor on "Proton therapy re-irradiation outcomes and genomic landscape of patients with recurrent head and neck cancer".
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Prasad M, Sekar R, and Murugan R
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- Humans, Genomics methods, Treatment Outcome, Head and Neck Neoplasms radiotherapy, Head and Neck Neoplasms genetics, Proton Therapy methods, Neoplasm Recurrence, Local genetics, Re-Irradiation methods
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2024
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7. A Rare Case Report of Fanconi Anemia-Associated Nuclease 1 Mutation Causing Nephrotic Syndrome.
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Sekar R, Rajakumar I, Mathew GG, Lamech T, and Jayaprakash V
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A 25-year-old African male patient presented with a history of frothy urination for one month. He had a significant family history of early onset chronic kidney disease (CKD) in his older brother. On evaluation, he was found to have deranged renal function and nephrotic-range proteinuria of 6152 mg/day. Urine examination revealed proteinuria and glycosuria. Viral serology and autoimmune screening results were negative. Ultrasonography revealed contracted kidneys that were not amenable to biopsy. Genetic analysis revealed a Fanconi anemia-associated nuclease 1 (FAN 1) mutation in exon 4 (c.1399G>A) and exon 12 (c.2786A>C). The patient was managed conservatively with a maximum dose of angiotensin receptor blockers with a reduction in proteinuria on follow-up. This case report highlights the rare manifestation of FAN 1 mutation and its variable effects on the kidney., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sekar et al.)
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- 2024
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8. Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of metabolic dysfunction-associated steatotic liver disease.
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Kwon Y, Gottmann P, Wang S, Tissink J, Motzler K, Sekar R, Albrecht W, Cadenas C, Hengstler JG, Schürmann A, and Zeigerer A
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Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Owing to limited available treatment options, novel pre-clinical models for target selection and drug validation are warranted. We have established and extensively characterized a primary human steatotic hepatocyte in vitro model system that could guide the development of treatment strategies for MASLD., Methods: Cryopreserved primary human hepatocytes from five donors varying in sex and ethnicity were cultured with free fatty acids in a 3D collagen sandwich for 7 days and the development of MASLD was followed by assessing classical hepatocellular functions. As proof of concept, the effects of the drug firsocostat (GS-0976) on in vitro MASLD phenotypes were evaluated., Results: Incubation with free fatty acids induced steatosis, insulin resistance, mitochondrial dysfunction, inflammation, and alterations in prominent human gene signatures similar to patients with MASLD, indicating the recapitulation of human MASLD in this system. The application of firsocostat rescued clinically observed fatty liver disease pathologies, highlighting the ability of the in vitro system to test the efficacy and potentially characterize the mode of action of drug candidates., Conclusions: Altogether, our human MASLD in vitro model system could guide the development and validation of novel targets and drugs for the treatment of MASLD., Impact and Implications: Due to low drug efficacy and high toxicity, clinical treatment options for metabolic dysfunction-associated steatotic liver disease (MASLD) are currently limited. To facilitate earlier stop-go decisions in drug development, we have established a primary human steatotic hepatocyte in vitro model. As the model recapitulates clinically relevant MASLD characteristics at high phenotypic resolution, it can serve as a pre-screening platform and guide target identification and validation in MASLD therapy., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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9. Telemedicine for Multidisciplinary Urologic Cancer Care: A Prospective Single Institution Study.
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Okoye F, Gadzinski AJ, Sekar R, Abarro I, Grivas P, Tykodi SS, Liao J, Chen J, Zeng J, Wright J, and Gore JL
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- Humans, Male, Female, Prospective Studies, Aged, Middle Aged, Patient Satisfaction, Aged, 80 and over, Patient Reported Outcome Measures, SARS-CoV-2, Surveys and Questionnaires, Telemedicine, COVID-19 epidemiology, Urologic Neoplasms therapy
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Background: We rapidly implemented a telemedicine Multidisciplinary Urologic Cancer Clinic (MDUCC) at the University of Washington/Seattle Cancer Care Alliance during the peak of the COVID-19 Public Health Emergency to maintain our ability to provide multidisciplinary cancer care. We report our experiences though assessment of patient-reported outcomes from our telemedicine MDUCC., Methods: Video visits with a urologic oncologist, medical oncologist, and radiation oncologist were conducted in the same format as our in-person MDUCC. We prospectively collected patient demographic and clinical data. Patients were invited to complete a post-visit survey that assessed satisfaction, provider trust, travel time, and costs of the telemedicine visit. We estimated travel distances and times from each patient's home to our clinic., Results: Among invited patients, twenty-four patients completed a survey after their telemedicine MDUCC visit. Twenty patients (83%) were at home during the visit. Most (85%) were men, Caucasian (79%), and were being seen in our Bladder Cancer MDUCC (83%). All twenty-four patients responded that they would be willing to have future appointments via telemedicine; eighteen patients (75%) strongly agreed that the encounter was high quality; 19 patients strongly agreed that they were satisfied with their visit. Patients saved an estimated average one-way travel distance of 145 miles and one-way travel time of 179 minutes to convene a telemedicine visit., Conclusions: Telemedicine MDUCCs are feasible and effective in providing access to multidisciplinary urologic cancer care. Patient satisfaction was high, and many patients were spared a substantial travel burden. Telemedicine may continue to be leveraged to improve access to multidisciplinary urologic cancer care., (Published by Elsevier Inc.)
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- 2024
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10. Algicidal activity synchronized with nitrogen removal by actinomycetes: Algicidal mechanism, stress response of algal cells, denitrification performance, and indigenous bacterial community co-occurrence.
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Ma B, Li A, Chen S, Guo H, Li N, Pan S, Chen K, Liu H, Kosolapov DB, Liu X, Zhi W, Chen Z, Mo Y, Sekar R, Huang T, and Zhang H
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- Nitrogen metabolism, Streptomyces metabolism, Nitrates metabolism, Photosynthesis, Denitrification, Microcystis metabolism, Harmful Algal Bloom
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The harmful algal blooms (HABs) can damage the ecological equilibrium of aquatic ecosystems and threaten human health. The bio-degradation of algal by algicidal bacteria is an environmentally friendly and economical approach to control HABs. This study applied an aerobic denitrification synchronization algicidal strain Streptomyces sp. LJH-12-1 (L1) to control HABs. The cell-free filtrate of the strain L1 showed a great algolytic effect on bloom-forming cyanobacterium, Microcystis aeruginosa (M. aeruginosa). The optimal algicidal property of strain L1 was indirect light-dependent algicidal with an algicidal rate of 85.0%. The functional metabolism, light-trapping, light-transfer efficiency, the content of pigments, and inhibition of photosynthesis of M. aeruginosa decreased after the addition of the supernatant of the strain L1 due to oxidative stress. Moreover, 96.05% nitrate removal rate synchronized with algicidal activity was achieved with the strain L1. The relative abundance of N cycling functional genes significantly increased during the strain L1 effect on M. aeruginosa. The algicidal efficiency of the strain L1 in the raw water was 76.70% with nitrate removal efficiency of 81.4%. Overall, this study provides a novel route to apply bacterial strain with the property of denitrification coupled with algicidal activity in treating micro-polluted water bodies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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11. Emerging Trends of Gold Nanostructures for Point-of-Care Biosensor-Based Detection of COVID-19.
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Yadav AK, Basavegowda N, Shirin S, Raju S, Sekar R, Somu P, Uthappa UT, and Abdi G
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In 2019, a worldwide pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged. SARS-CoV-2 is the deadly microorganism responsible for coronavirus disease 2019 (COVID-19), which has caused millions of deaths and irreversible health problems worldwide. To restrict the spread of SARS-CoV-2, accurate detection of COVID-19 is essential for the identification and control of infected cases. Although recent detection technologies such as the real-time polymerase chain reaction delivers an accurate diagnosis of SARS-CoV-2, they require a long processing duration, expensive equipment, and highly skilled personnel. Therefore, a rapid diagnosis with accurate results is indispensable to offer effective disease suppression. Nanotechnology is the backbone of current science and technology developments including nanoparticles (NPs) that can biomimic the corona and develop deep interaction with its proteins because of their identical structures on the nanoscale. Various NPs have been extensively applied in numerous medical applications, including implants, biosensors, drug delivery, and bioimaging. Among them, point-of-care biosensors mediated with gold nanoparticles (GNPSs) have received great attention due to their accurate sensing characteristics, which are widely used in the detection of amino acids, enzymes, DNA, and RNA in samples. GNPS have reconstructed the biomedical application of biosensors because of its outstanding physicochemical characteristics. This review provides an overview of emerging trends in GNP-mediated point-of-care biosensor strategies for diagnosing various mutated forms of human coronaviruses that incorporate different transducers and biomarkers. The review also specifically highlights trends in gold nanobiosensors for coronavirus detection, ranging from the initial COVID-19 outbreak to its subsequent evolution into a pandemic., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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12. High factor VIII concentrations interfere with glycoprotein VI-mediated platelet activation in vitro.
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Sekar R, Mimoun A, Bou-Jaoudeh M, Loyau S, Delignat S, Daventure V, Bonilla P, Bhale AS, Venkataraman K, Rayes J, Boulaftali Y, Jandrot-Perrus M, Proulle V, and Lacroix-Desmazes S
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- Humans, Phosphorylation, Collagen metabolism, Protein Binding, Flow Cytometry, Thrombin metabolism, Dose-Response Relationship, Drug, Microscopy, Confocal, Platelet Membrane Glycoproteins metabolism, Platelet Activation drug effects, Blood Platelets metabolism, Factor VIII metabolism, Platelet Aggregation
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Background: The recruitment of activated factor VIII (FVIII) at the surface of activated platelets is a key step toward the burst of thrombin and fibrin generation during thrombus formation at the site of vascular injury. It involves binding to phosphatidylserine and, possibly, to fibrin-bound α
IIb β3 . Seminal work had shown the binding of FVIII to resting platelets, yet without a clear understanding of a putative physiological relevance., Objectives: To characterize the effects of FVIII-platelet interaction and its potential modulation of platelet function., Methods: FVIII was incubated with washed platelets. The effects on platelet activation (spontaneously or triggered by collagen and thrombin) were studied by flow cytometry and light transmission aggregometry. We explored the involvement of downstream pathways by studying phosphorylation profiles (Western blot). The FVIII-glycoprotein (GP) VI interaction was investigated by ELISA, confocal microscopy, and proximity ligation assay., Results: FVIII bound to the surface of resting and activated platelets in a dose-dependent manner. FVIII at supraphysiological concentrations did not induce platelet activation but rather specifically inhibited collagen-induced platelet aggregation and altered glycoprotein VI (GPVI)-dependent phosphorylation. FVIII, freed of its chaperone protein von Willebrand factor (VWF), interacted in close proximity with GPVI at the platelet surface., Conclusion: We showed that VWF-free FVIII binding to, or close to, GPVI modulates platelet activation in vitro. This may represent an uncharacterized negative feedback loop to control overt platelet activation. Whether locally activated FVIII concentrations achieved during platelet accumulation and thrombus formation at the site of vascular injury in vivo are compatible with such a function remains to be determined., Competing Interests: Declaration of competing interests The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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13. Fibrinolysis and clinical outcomes in acute pulmonary embolism. Madras medical college pulmonary embolism (M-PER) registry from India.
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Gnanaraj JP, Jaganathan V, Asaithambi N, Sekar R, Chandrasekaran E, Elangovan EM, Srinivasan K, Ganesan M, Mohandoss NP, Gorijavaram PK, Ramesh R, Raji R, Kunjitham T, Kaliamoorthy T, Sangareddi V, and Mohanan N
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- Humans, Female, Male, India epidemiology, Middle Aged, Prospective Studies, Acute Disease, Echocardiography, Survival Rate trends, Thrombolytic Therapy methods, Follow-Up Studies, Prognosis, Fibrinolysis physiology, Adult, Risk Factors, Fibrinolytic Agents therapeutic use, Pulmonary Embolism diagnosis, Pulmonary Embolism mortality, Pulmonary Embolism epidemiology, Registries, Hospital Mortality trends, Electrocardiography
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Background: Acute pulmonary embolism (APE) is the third most common cause of vascular death. Data on APE from India and other low-and middle-income countries is sparse., Objectives: Study the clinical characteristics, prognostic factors, in-hospital mortality (IMH) and 12 months mortality of patients with APE in India., Methods: We prospectively enrolled 186 consecutive patients diagnosed with APE between November 2016 and November 2021 in Madras Medical College Pulmonary Embolism Registry (M-PER). All patients had electrocardiography and echocardiography. High risk patients and selected intermediate risk patients underwent fibrinolysis., Results: 75 % of our patients were below 50 years of age. 35 % were women. The mean time to presentation from symptom onset was 6.04 ± 10.01 days. 92 % had CT pulmonary angiography. Intermediate risk category (61.3 %) was the more common presentation followed by high risk (26.9 %). Electrocardiography showed S1Q3T3 pattern in 56 %. 76 % had right ventricular dysfunction and 12.4 % had right heart thrombi(RHT) by echocardiography. 50.5 % received fibrinolysis. Patients with RHT received fibrinolysis more frequently (78.3 % vs 46.6 %; p = 0.007). In-hospital mortality (IHM) was 15.6 %. Systemic arterial desaturation and need for mechanical ventilation independently predicted IHM. Ten patients (5.3 %) were lost to follow up. One year mortality was 26.7 % (47/176). One year mortality of patients discharged alive was similar among high, intermediate and low risk groups(14.8 % vs 1.9 % vs 10.5 %; p = 0.891)., Conclusions: Patients with PE are often young and present late in India. The in-hospital and 12 months mortality were high. Low and intermediate risk groups had a high post discharge mortality similar to high risk patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)
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- 2024
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14. PI3K/AKT Signaling Pathway Mediated Autophagy in Oral Carcinoma - A Comprehensive Review.
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Rajendran P, Sekar R, Dhayasankar PS, Ali EM, Abdelsalam SA, Balaraman S, Chellappan BV, Metwally AM, and Abdallah BM
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- Humans, Apoptosis, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, TOR Serine-Threonine Kinases metabolism, Autophagy physiology, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell genetics, Mouth Neoplasms pathology, Mouth Neoplasms metabolism, Mouth Neoplasms drug therapy, Signal Transduction
- Abstract
Oral cancer is the most heterogeneous cancer at clinical and histological levels. PI3K/AKT/mTOR pathway was identified as one of the most commonly modulated signals in oral cancer, which regulates major cellular and metabolic activity of the cell. Thus, various proteins of PI3K/AKT/mTOR pathway were used as therapeutic targets for oral cancer, to design more specific drugs with less off-target toxicity. This review sheds light on the regulation of PI3K/AKT/mTOR, and its role in controlling autophagy and associated apoptosis during the progression and metastasis of oral squamous type of malignancy (OSCC). In addition, we reviewed in detail the upstream activators and the downstream effectors of PI3K/AKT/mTOR signaling as potential therapeutic targets for oral cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
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- 2024
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15. An Uncommon Salivary Gland Swelling- Parotid Duct Cyst and Its Management.
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Begum B, Sekar R, Raja K, and Stephen N
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Cysts in the parotid region are more common in the gland than in the duct. Isolated cyst of parotid duct is a rare presentation. The treatment for most of the cystic lesions of the parotid or the parotid duct is the excision of the cyst with superficial parotidectomy. However, these lesions can be approached intra-orally for marsupialization achieving the same surgical results with less morbidity. This paper presents a rare case of parotid duct cyst which was managed by intraoral drainage and marsupialization. A 53-year-old female presented with swelling in the right cheek, associated with frequent fluid drainage inside the oral cavity for four months. Radiology and Fine needle aspiration revealed a benign parotid duct cyst with normal parotid gland. It was managed by a simple surgical technique of marsupialization. The patient was followed up for 1 year with no evidence of recurrence. Marsupialization obviates the need for parotidectomy in the simple cystic lesion of the parotid duct, unlike the cystic lesion in the gland per se and also reduces risk of recurrence. The simplicity and lack of major complications make it an effective treatment for salivary duct cysts., Competing Interests: Conflict of interestThe authors declare that there are no conflict of interest., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2024
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16. Epigenetic modulation of long noncoding RNA H19 in oral squamous cell carcinoma-A narrative review.
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Rajendran P, Sekar R, Abdallah BM, Fathima Jh S, Ali EM, Jayaraman S, Abdelsalam SA, and Veeraraghavan V
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Oral squamous cell carcinoma (OSCC) showed a seemingly increasing incidence in the last decade. In India, despite the use of tobacco decreased rapidly, in the past five years, the incidence pattern of OSCC over gender and age showed a drastic shift. About 51 % of the head and neck cancers are not associated with habits. Studies exploring various contributing factors in the incidence of this malignancy have documented. Recently, the epigenetic factors associated with the induction and progression of OSCC were explored. More than 90 % of the human genome is made up of non-coding transcriptome, which believed to be noises. However, these non-coding RNAs were identified to be the major epigenetic modulators, which raises concern over incidence of carcinoma in non-habit patients. H19 is a long non coding RNA which proved to be an effective biomarker in various carcinoma. Its role in oral squamous cell cancer was not investigated in depth. This review discusses in detail the various epigenetic role of H19 in inducing oral carcinogenesis., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)
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- 2024
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17. Bibliometric analysis of research on dental age estimation.
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Ponraj S, Ramar K, Sekar R, and Kasi A
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- Humans, China, Anthropology, External Fixators, Bibliometrics, Academies and Institutes
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Dental age estimation plays a key role in therapeutic, medicolegal, forensic, and anthropological applications. The purpose of this study is to evaluate the research progress on dental age estimation using bibliometric analysis. Data were gathered from Scopus, Web of Science and PubMed. Keyword co-occurrence analysis, collaboration network analysis, and descriptive analysis of bibliographic data were all completed using VOS viewer and Biblioshiny software. There has been an ongoing but gradual rise in research regarding dental age estimation, with notable increase since 2014. The country with the most publications published (205) was India. The year of 2018 (TP = 92) and 2021 (TP = 100) saw a rapid spike in publications and citations, respectively. The Shanghai Jiao Tong University School of Medicine, which has 153 citations, was the most productive institution. Forensic Science International was the journal with the greatest number of publications (73). Author Cameriere had the maximum number of publications (30). The increase in publications associated to collaboration across numerous authors, nations, and institutes serves as evidence of the significant improvement in dental age estimation. This citation analysis allows for the identification of the most relevant and pertinent research fields while providing a view on the development of research in the field of dental age estimation.
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- 2023
18. Langerhans Cell Histiocytosis of the Nose and Maxilla: A Rare Presentation.
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Sekar R and Raja K
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Langerhans cell histiocytosis (LCH) is a disease characterized by localized and generalized proliferation of the histiocytes. It is a locally aggressive condition. The clinical presentation is highly variable and can range from isolated, self-healing skin or bone lesions to life-threatening multisystem disease. It can present as a unifocal or multifocal disease. The majority are present in the head and neck region, but the involvement of Paranasal sinuses is rare. Here we describe a 64-years-old female who presented with a slow-growing left nasal mass for 1 year. Evaluation of the patient was suggestive of malignancy, but the biopsy report turned out to be Langerhans cell histiocytosis; subsequently left, total maxillectomy was done. We hereby present a unique case of LCH with isolated nose and paranasal sinus involvement., Competing Interests: Conflict of interestThe authors declare that there are no conflict of interest., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2023
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19. Multiomic integration reveals neuronal-extracellular vesicle coordination of gliotic responses in degeneration.
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Cioanca AV, Wooff Y, Aggio-Bruce R, Sekar R, Dietrich C, and Natoli R
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- Mice, Animals, Multiomics, Neurons metabolism, Inflammation metabolism, Extracellular Vesicles, MicroRNAs genetics, MicroRNAs metabolism
- Abstract
In the central nervous system (CNS), including in the retina, neuronal-to-glial communication is critical for maintaining tissue homeostasis including signal transmission, transfer of trophic factors, and in the modulation of inflammation. Extracellular vesicle (EV)-mediated transport of molecular messages to regulate these processes has been suggested as a mechanism by which bidirectional communication between neuronal and glial cells can occur. In this work we employed multiomics integration to investigate the role of EV communication pathways from neurons to glial cells within the CNS, using the mouse retina as a readily accessible representative CNS tissue. Further, using a well-established model of degeneration, we aimed to uncover how dysregulation of homeostatic messaging between neurons and glia via EV can result in retinal and neurodegenerative diseases. EV proteomics, glia microRNA (miRNA) Open Array and small RNA sequencing, and retinal single cell sequencing were performed, with datasets integrated and analysed computationally. Results demonstrated that exogenous transfer of neuronal miRNA to glial cells was mediated by EV and occurred as a targeted response during degeneration to modulate gliotic inflammation. Taken together, our results support a model of neuronal-to-glial communication via EV, which could be harnessed for therapeutic targeting to slow the progression of retinal-, and neuro-degenerations of the CNS., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
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- 2023
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20. Impairing Gasdermin D-mediated pyroptosis is protective against retinal degeneration.
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Sekar R, Wooff Y, Cioanca AV, Kurera M, Ngo C, Man SM, and Natoli R
- Subjects
- Animals, Mice, Cytokines metabolism, Gasdermins, Inflammasomes metabolism, Inflammation, Interleukin-1beta metabolism, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Pyroptosis physiology, Retinal Degeneration
- Abstract
Background: Inflammasome activation and the subsequent release of pro-inflammatory cytokines including Interleukin 1β (IL-1β) have been widely reported to contribute to the progression of retinal degenerations, including age-related macular degeneration (AMD), the leading cause of blindness in the Western World. The role of Gasdermin D (GSDMD), a key executioner of pyroptosis following inflammasome activation, however, is less well-established. In this study we aimed to characterise the role of GSDMD in the healthy and degenerating retina, and uncover its role as a conduit for IL-1β release, including via extracellular vesicle (EV)-mediated release., Methods: GSDMD mutant and knockout mice, in vitro models of inflammation and a well-established in vivo model of retinal degeneration (photo-oxidative damage; PD) were utilised to explore the role and pathological contribution of GSDMD in regulating IL-1β release and propagating retinal inflammation. RNA sequencing of whole retinas was used to investigate GSDMD-mediated inflammation during degeneration. The role of EVs in GSDMD-mediated IL-1β release was investigated using nanoparticle tracking analysis, ELISA and EV inhibition paradigms. Finally, the therapeutic efficacy of targeting GSDMD was examined using GSDMD-specific siRNA., Results: We identified in this work that mice deficient in GSDMD had better-preserved retinal function, increased photoreceptor survivability and reduced inflammation. RNA-Seq analysis revealed that GSDMD may propagate inflammation in the retina via NF-κB signalling cascades and release of pro-inflammatory cytokines. We also showed that IL-1β was packaged and released via EV in a GSDMD-dependent manner. Finally, we demonstrated that impairing GSDMD function using RNAi or blocking EV release was able to reduce IL-1β content in cell-free supernatant and EV., Conclusions: Taken together, these results suggest that pyroptotic pore-forming protein GSDMD plays a key role in the propagation of retinal inflammation, in particular via the release of EV-encapsulated IL-1β. Targeting GSDMD using genetic or pharmacological inhibitors may pose a therapeutic opportunity to dampen inflammatory cascades and delay the progression of retinal degeneration., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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21. Factors associated with higher risk of small-for-gestational-age infants in women treated for gestational diabetes.
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Drever HJ, Davidson SJ, Callaway LK, Sekar R, and DE Jersey SJ
- Abstract
Background: Previously, management of gestational diabetes (GDM) has focused largely on glycaemic control, with a view to reduce the occurrence of large-for-gestational-age (LGA) infants. However, tight glycaemic control in GDM is associated with a higher incidence of small-for-gestational-age (SGA) infants, which has been linked to higher rates of adverse outcomes., Aim: The aim was to characterise risk factors associated with having an SGA infant in women being treated for GDM., Methods: This was a retrospective observational cohort study of 308 women with GDM. Women were split into groups based on their infant's size at delivery (SGA, appropriate-for-gestational-age (AGA) or LGA). Literature review and expert opinion helped to determine several predictors of women with GDM delivering an SGA infant, and statistical analysis was used to produce odds ratios (OR) for these predictors., Results: The sample included primiparous women with a mean pre-pregnancy body mass index (BMI) of 25.72 (standard deviation: 5.75). Metabolic risk factors associated with delivering an SGA infant included a lower pre-pregnancy BMI (adjusted OR 1.13, P = 0.04, 95% confidence interval (CI): 1.01-1.26), a lower fasting blood glucose level (BGL) (adjusted OR: 3.21, P = 0.01, 95% CI: 1.30-7.93) and growth that was high risk for SGA at baseline ultrasound scan (USS) (adjusted OR: 7.43, P < 0.001, 95% CI: 2.93-18.79)., Conclusions: The combined clinical picture of lower pre-pregnancy BMI, fasting BGL and baseline USS growth measurements may indicate a need for less aggressive glucose management in women with GDM to prevent SGA infants., (© 2023 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)
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- 2023
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22. Transoral Robotic Excision of Paediatric Lingual Thyroglossal Duct Cyst.
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Das S, Sekar R, Alexander A, and Ganesan S
- Abstract
Lingual thyroglossal duct cyst (TGDC) is a rare variant of TGDC that emerges within the tongue base. It presents a unique surgical challenge. There are different approaches to managing this condition. Transoral robotic surgery (TORS) has been successfully used for lesions of the tongue base in adults. This report presents a 7 year old boy with a cystic lesion in the base of tongue, which was diagnosed to be a lingual TGDC. The cyst was excised transorally using Da Vinci Robotic system. The surgery was performed in a short operating time with no complications or recurrence on follow up. TORS is an effective and reliable method of excision of lingual TGDC in the paediatric population. Lingual TGDC can be managed by simple excision of the cyst without excision of hyoid bone. Further studies are needed to confirm the safety and recurrence rates of this technique in paediatric population., Competing Interests: Conflict of interestThe authors declare that there are no conflict of interest., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2023
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23. Editorial: Metabolism in nonalcoholic fatty liver disease.
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Najjar SM, Ghadieh HE, Sekar R, Carraro R, Noriega LG, and Paes AMA
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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- 2023
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24. Kaposiform Haemangioendothelioma of the Sublingual Gland in an Adult.
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Chowdhary S, Sekar R, Saxena SK, and Badhe B
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Kaposiform haemangioendotheliomas (KHE) are extremely rare, borderline malignant, locally aggressive vascular tumours. KHE is usually found in the retroperitoneum, over the extremities, the soft tissues of the trunk, mediastinum and the head and neck regions. We present a very rare case of KHE of the sublingual gland in an adult, which was not associated with Kasabach-Merritt phenomenon and was resected completely without any recurrence. To the best of our knowledge, this is the first reported case in the literature of a KHE arising from the salivary glands in an adult., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest regarding the publication of this paper., (© Association of Otolaryngologists of India 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2023
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25. Salivaomics to decode non-coding RNAs in oral cancer. A narrative review.
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Rajendran P, Sekar R, Zahra HA, Jayaraman S, Rajagopal P, Abdallah BM, Ali EM, Abdelsalam SA, and Veeraraghavan V
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Oral cancer is the most debilitating disease which affects the orderly life of a human. With so much advancement in research and technology, the average life expectancy of an individual with oral cancer appears to be about 5 years. The changing trend in incidence of oral cancer among young individuals and women without tobacco habits are ascending. Non habit related oral cancer are taking centre stage and multiple factors which induce complex biology are associated in such scenarios. To decipher the aetiology and to understand the process, these cancerous conditions are to be studied at molecular level. Saliva, the most non-invasively obtained body fluid are assessed for biomarkers exclusively in liquid biopsy. This fluid gives a huge platform to study number of molecules associated with oral cancer. Non coding RNAs are transcripts with no protein coding function. They are gaining more importance in recent times. Long noncoding RNA, microRNA are major types of noncoding transcriptome that influences in progression of oral cancer. They seem to play an important role in health and disease. Apart from these, circulating tumour cells, exosomes, extracellular vesicles, antigens and other proteins can be studied from saliva. This review is aimed to update the knowledge on current biomarkers in saliva associated with oral cancer and their epigenetic role in disease progression as well recent advances in detecting these markers to identify the stage of the disease, which will help in deciding the treatment protocol., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)
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- 2023
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26. Quantification of Helicobacter pylori and its oncoproteins in the oral cavity: A cross-sectional study.
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Sekar R, Murali P, and Junaid M
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- Humans, Bacterial Proteins genetics, Antigens, Bacterial genetics, Cross-Sectional Studies, Oncogene Proteins, Genotype, Helicobacter pylori, Stomach Neoplasms, Periodontitis, Dental Plaque, Mouth Neoplasms, Gingivitis
- Abstract
Objective: To identify Helicobacter pylori (H. pylori) and related oncogenic and virulent proteins (CagA and VacA) in patients with gingivitis, periodontitis, oral cancer and gastric cancer., Methods: Subgingival plaque samples were collected from 90 individuals with either gingivitis/periodontitis (group A, n = 30), oral cancer (group B, n = 30) and gastric cancer (group C, n = 30). H. pylori was identified by real-time polymerase chain reaction (RT-PCR). The virulent organisms were detected by identification of proteins CagA and VacA through Enzyme Linked Immuno-Sorbent Assay (ELISA)., Results: We identified the presence of H. pylori in subgingival plaque samples among a large majority (76/90) of our study cohort. The proportions of CagA and VacA identified among H. pylori individuals with periodontal inflammation and oral cancer were lower than those diagnosed with gastric cancer. Furthermore, the relative risk of oral cancer based on the presence of the organism was no different to those with gingivitis/periodontitis., Conclusion: The findings of our study do not indicate significant association between the organism and oral cancer, but preludes that the oral cavity could act as a potential niche for H. pylori. The possibility for CagA and VacA proteins to be pathogenic in oral cavity is highly possible and must be researched extensively., (© 2022 Wiley Periodicals LLC.)
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- 2023
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27. Short exposure to photo-oxidative damage triggers molecular signals indicative of early retinal degeneration.
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Wooff Y, Cioanca AV, Wills E, Chu-Tan JA, Sekar R, and Natoli R
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- Mice, Animals, Disease Models, Animal, Mice, Inbred C57BL, Oxidative Stress, Retinal Degeneration metabolism, Macular Degeneration, MicroRNAs genetics, MicroRNAs metabolism, Geographic Atrophy
- Abstract
Introduction: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, currently affecting over 350 billion people globally. For the most prevalent late-stage form of this disease, atrophic AMD, there are no available prevention strategies or treatments, in part due to inherent difficulties in early-stage diagnosis. Photo-oxidative damage is a well-established model for studying inflammatory and cell death features that occur in late-stage atrophic AMD, however to date has not been investigated as a potential model for studying early features of disease onset. Therefore, in this study we aimed to determine if short exposure to photo-oxidative damage could be used to induce early retinal molecular changes and advance this as a potential model for studying early-stage AMD., Methods: C57BL/6J mice were exposed to 1, 3, 6, 12, or 24h photo-oxidative damage (PD) using 100k lux bright white light. Mice were compared to dim-reared (DR) healthy controls as well as mice which had undergone long periods of photo-oxidative damage (3d and 5d-PD) as known timepoints for inducing late-stage retinal degeneration pathologies. Cell death and retinal inflammation were measured using immunohistochemistry and qRT-PCR. To identify retinal molecular changes, retinal lysates were sent for RNA sequencing, following which bioinformatics analyses including differential expression and pathway analyses were performed. Finally, to investigate modulations in gene regulation as a consequence of degeneration, microRNA (miRNA) expression patterns were quantified using qRT-PCR and visualized using in situ hybridization., Results: Short exposure to photo-oxidative damage (1-24h-PD) induced early molecular changes in the retina, with progressive downregulation of homeostatic pathways including metabolism, transport and phototransduction observed across this time-course. Inflammatory pathway upregulation was observed from 3h-PD, preceding observable levels of microglia/macrophage activation which was noted from 6h-PD, as well as significant photoreceptor row loss from 24h-PD. Further rapid and dynamic movement of inflammatory regulator miRNA, miR-124-3p and miR-155-5p, was visualized in the retina in response to degeneration., Conclusion: These results support the use of short exposure to photo-oxidative damage as a model of early AMD and suggest that early inflammatory changes in the retina may contribute to pathological features of AMD progression including immune cell activation and photoreceptor cell death. We suggest that early intervention of these inflammatory pathways by targeting miRNA such as miR-124-3p and miR-155-5p or their target genes may prevent progression into late-stage pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interests., (Copyright © 2023 Wooff, Cioanca, Wills, Chu-Tan, Sekar and Natoli.)
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- 2023
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28. Evaluation of Remineralization Potential of Natural Substances on Artificially Induced Carious Lesions in Primary Teeth: An In Vitro Study.
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Ravi PV, Sekar R, and Ramar K
- Abstract
Aim: To evaluate the remineralizing potential of natural substances on artificially induced caries lesions in primary teeth., Materials and Methods: A total of 50 primary molar teeth were selected and subjected to a demineralization process. Then samples were randomly divided into five groups for the remineralization process. Group I-colophony, group II-5% sodium fluoride (NaF) + colophony, group III-grape seed extract (GSE) + colophony, group IV-5% NaF + colophony + 10% peptide, and group V- GSE + colophony + 10% peptide. All the groups were subjected to remineralization using a brushing stimulator for 3,000 cycles. Assessment was done using Vickers hardness testing machine for evaluating the enamel surface microhardness (SMH) and scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDX) for evaluating the surface morphology and mineral content, before and after demineralization and after remineralization, the obtained data was analyzed statistically using IBM Statistical Package for the Social Sciences (SPSS) software version 25., Results: The enamel microhardness results of this study revealed that remineralization of enamel was highest in group V (212.83 ± 64.416) and least in group II (137.83 ± 26.324) p -value of 0.038. SEM-EDX analysis revealed high calcium (Ca) and fluoride (F) content in groups II and IV, which was significant ( p -value of 0.001) from other groups. Surface morphology evaluated with SEM revealed spherical globular agglomerates and scaffolding deposits on the enamel surface in groups III and V resembling the remineralization process., Conclusion: Grape seed extract (GSE) with colophony and peptide is a superior natural alternative to NaF. Colophony also exhibited remineralizing potential in primary enamel., Clinical Significance: Natural remineralizing agents like GSE, colophony, and its combination serves as a potential alternative to overcome the toxic effect on long-term usage of F. These natural substances can be applicable in clinical conditions by incorporating toothpaste and varnish, which can be used as an alternative or adjuvant to the topical application of F., How to Cite This Article: Pooja V Ravi, Rajakumar S, Kavitha Ramar. Evaluation of Remineralization Potential of Natural Substances on Artificially Induced Carious Lesions in Primary Teeth: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(2):244-250., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)
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- 2023
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29. Accumulation, Chronicity, and Induction of Oxidative Stress Regulating Genes Through Allium cepa L. Functionalized Silver Nanoparticles in Freshwater Common Carp (Cyprinus carpio).
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Krishnasamy Sekar R, Arunachalam R, Anbazhagan M, Palaniyappan S, Veeran S, Sridhar A, and Ramasamy T
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- Animals, Onions genetics, Onions metabolism, Silver metabolism, Spectroscopy, Fourier Transform Infrared, Oxidative Stress, Fresh Water, Gills metabolism, Carps genetics, Carps metabolism, Metal Nanoparticles, Water Pollutants, Chemical metabolism
- Abstract
Green evolutionary products such as biologically fabricated nanoparticles (NPs) pose a hazard to aquatic creatures. Herein, biogenic silver nanoparticles (AgNPs) were synthesized by the reaction between ionic silver (AgNO
3 ) and aqueous onion peel extract (Allium cepa L). The synthesized biogenic AgNPs were characterized with UV-Visible spectrophotometer, XRD, FT-IR, and TEM with EDS analysis; then, their toxicity was assessed on common carp fish (Cyprinus carpio) using biomarkers of haematological alterations, oxidative stress, histological changes, differential gene expression patterns, and bioaccumulation. The 96 h lethal toxicity was analysed with various concentrations (2, 4, 6, 8, and 10 mg/l) of biogenic AgNPs. Based on 96 h LC50 , sublethal concentrations (1/15th , 1/10th , and 1/5th ) were given to C. carpio for 28 days. At the end of experiment, the bioaccumulations of Ag content were accumulated mainly in the gills, followed by the liver and muscle. At an interval of 7 days, the haematological alterations showed significance (p < 0.05) and elevation of antioxidant defence mechanism reveals the toxicity of biogenic synthesized AgNPs. Adverse effects on oxidative stress were probably related to the histopathological damage of its vital organs like gill, liver, and muscle. Finally, the fish treated with biogenic synthesized AgNPs were significantly (p < 0.05) downregulates the oxidative stress genes such as Cu-Zn SOD, CAT, GPx1a, GST-α, CYP1A, and Nrf-2 expression patterns. The present study provides evidence of biogenic synthesized AgNPs influence on the aquatic life through induction of oxidative stress., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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30. Recent Progress of Gold-Based Nanostructures towards Future Emblem of Photo-Triggered Cancer Theranostics: A Special Focus on Combinatorial Phototherapies.
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Sekar R, Basavegowda N, Thathapudi JJ, Sekhar MR, Joshi P, Somu P, and Baek KH
- Abstract
Cancer is one of the most dangerous health problems in the millennium and it is the third foremost human cause of death in the universe. Traditional cancer treatments face several disadvantages and cannot often afford adequate outcomes. It has been exhibited that the outcome of several therapies can be improved when associated with nanostructures. In addition, a modern tendency is being developed in cancer therapy to convert single-modal into multi-modal therapies with the help of existing various nanostructures. Among them, gold is the most successful nanostructure for biomedical applications due to its flexibility in preparation, stabilization, surface modifications, less cytotoxicity, and ease of bio-detection. In the past few decades, gold-based nanomaterials rule cancer treatment applications, currently, gold nanostructures were the leading nanomaterials for synergetic cancer therapies. In this review article, the synthesis, stabilization, and optical properties of gold nanostructures have been discussed. Then, the surface modifications and targeting mechanisms of gold nanomaterials will be described. Recent signs of progress in the application of gold nanomaterials for synergetic cancer therapies such as photodynamic and photo-thermal therapies in combination with other common interventions such as radiotherapy, chemotherapy, and will be reviewed. Also, a summary of the pharmacokinetics of gold nanostructures will be delivered. Finally, the challenges and outlooks of the gold nanostructures in the clinics for applications in cancer treatments are debated.
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- 2023
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31. The Mycobacterium tuberculosis prolyl dipeptidyl peptidase cleaves the N-terminal peptide of the immunoprotein CXCL-10.
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Lioe TS, Xie Z, Wu J, Li W, Sun L, Feng Q, Sekar R, Tefsen B, and Ruiz-Carrillo D
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- Humans, Dipeptidyl Peptidase 4 chemistry, Dipeptidyl Peptidase 4 metabolism, Peptides, Serine Endopeptidases metabolism, Substrate Specificity, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Mycobacterium tuberculosis metabolism
- Abstract
Dipeptidyl peptidases constitute a class of non-classical serine proteases that regulate an array of biological functions, making them pharmacologically attractive enzymes. With this work, we identified and characterized a dipeptidyl peptidase from Mycobacterium tuberculosis (MtDPP) displaying a strong preference for proline residues at the P
1 substrate position and an unexpectedly high thermal stability. MtDPP was also characterized with alanine replacements of residues of its active site that yielded, for the most part, loss of catalysis. We show that MtDPP catalytic activity is inhibited by well-known human DPP4 inhibitors. Using MALDI-TOF mass spectrometry we also describe that in vitro , MtDPP mediates the truncation of the C-X-C motif chemokine ligand 10, indicating a plausible role in immune modulation for this mycobacterial enzyme., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)- Published
- 2023
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32. Recent Developments of Silk-Based Scaffolds for Tissue Engineering and Regenerative Medicine Applications: A Special Focus on the Advancement of 3D Printing.
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Shabbirahmed AM, Sekar R, Gomez LA, Sekhar MR, Hiruthyaswamy SP, Basavegowda N, and Somu P
- Abstract
Regenerative medicine has received potential attention around the globe, with improving cell performances, one of the necessary ideas for the advancements of regenerative medicine. It is crucial to enhance cell performances in the physiological system for drug release studies because the variation in cell environments between in vitro and in vivo develops a loop in drug estimation. On the other hand, tissue engineering is a potential path to integrate cells with scaffold biomaterials and produce growth factors to regenerate organs. Scaffold biomaterials are a prototype for tissue production and perform vital functions in tissue engineering. Silk fibroin is a natural fibrous polymer with significant usage in regenerative medicine because of the growing interest in leftovers for silk biomaterials in tissue engineering. Among various natural biopolymer-based biomaterials, silk fibroin-based biomaterials have attracted significant attention due to their outstanding mechanical properties, biocompatibility, hemocompatibility, and biodegradability for regenerative medicine and scaffold applications. This review article focused on highlighting the recent advancements of 3D printing in silk fibroin scaffold technologies for regenerative medicine and tissue engineering.
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- 2023
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33. Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes.
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Sekar R, Motzler K, Kwon Y, Novikoff A, Jülg J, Najafi B, Wang S, Warnke AL, Seitz S, Hass D, Gancheva S, Kahl S, Yang B, Finan B, Schwarz K, Okun JG, Roden M, Blüher M, Müller TD, Krahmer N, Behrends C, Plettenburg O, Miaczynska M, Herzig S, and Zeigerer A
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- 2022
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34. Migrated Foreign Body of Upper Digestive Tract-A Ten-Year Institutional Experience.
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Sekar R, Raja K, Ganesan S, Alexander A, and Saxena SK
- Abstract
The ingested foreign body is one of the commonest emergencies encountered by otolaryngologists Depending on the shape and duration of impaction, a small number of foreign bodies (1-2%) can perforate the wall of the gastrointestinal Tract. A migrated foreign body may remain quiescent or cause life-threatening suppurative and vascular complications. Data were collected retrospectively from the hospital records in a tertiary care hospital in South India from 2010 to 2020. Fifteen patients diagnosed with migrated foreign body and who underwent neck exploration were included in the study. Demographic details, mode of presentation, clinical and radiological findings, rigid esophagoscopy findings, neck exploration techniques employed were noted. The mean age of the patients was 37.66 years. All patients had a history of dysphagia, odynophagia, and point tenderness. All the patients underwent a lateral neck radiograph, and it was positive in 12 patients (80%), while in 3 patients (20%), it was negative. All the patients had a positive finding in Contrast-Enhanced Computed Tomography. Esophagoscopy was done prior to neck exploration to identify the site of injury and the probable site of migration. All the patients underwent lateral neck exploration, and foreign body was removed. Migrated foreign body can cause significant morbidity and mortality if not diagnosed and managed early. Strong suspicion and a systematic approach are needed for the diagnosis and management., Competing Interests: Conflict of InterestThe authors have no conflict of interest to disclose. The authors have no relevant financial or non-financial interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article., (© Association of Otolaryngologists of India 2021.)
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- 2022
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35. An Uncommon Differential for Mass in the Middle Ear Cleft-Temporal Meningoencephalocele.
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Das S, Sekar R, and Alexander A
- Abstract
Meningoencephalocoele (ME) of the temporal bone is otherwise known as brain fungus. It is a rare and potentially life-threatening condition. It occurs in cases of chronic otitis media either as a complication or iatrogenically induced following mastoid surgeries. It requires prompt surgical intervention. High-resolution Computer tomography of Temporal bone and Magnetic resonance imaging of the brain are needed to detect these cases. Surgery can be otological, neurosurgical, or combined. We discuss a case of Iatrogenic Temporal meningoencephalocele and its management along with a review of the literature., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2021.)
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- 2022
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36. Recurrent Giant Mucoepidermoid Carcinoma of the Parotid: A Case Report and Review of Literature.
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Nagi K, Sekar R, Ganesan S, Alexander A, and Saxena SK
- Abstract
Mucoepidermoid carcinoma is the most common salivary gland malignancy and about one third occurs in the parotid gland. The peak incidence is commonly seen between the third and fifth decades of life. It routinely presents as a fixed, painless mass below the ear. However, its presentation as a giant mass is exceedingly rare. Here, we report a case of a recurrent giant exophytic mucoepidermoid carcinoma in a young male. He underwent Revision Total Parotidectomy with Modified Radical neck dissection with Sural nerve grafting and an Anterolateral thigh flap reconstruction followed by Adjuvant radiotherapy. The rarity of the clinical presentation and the management challenges faced in a young male are being discussed in this case report., Competing Interests: Conflict of interestAll authors have declared that there is no conflict of interest among them., (© Association of Otolaryngologists of India 2021.)
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- 2022
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37. Microdebrider Assisted Resection of Suprastomal Lesions via Tracheostoma: A Novel Technique.
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Das S, Sekar R, Alexander A, and Saxena SK
- Abstract
Subglottic lesions are the commonest airway conditions leading to life threatening complications. Many conditions can present as subglottic lesions and can affect various age groups. There are various methods to manage these conditions described in the literature. We have devised a new method of managing these lesions by using a microdebrider inserted through the tracheal stoma. Here we describe three cases of subglottic lesions with pre-existing tracheostomy managed by this technique. The advantages and the post operative follow up of these patients are described. The follow up of the patients after 1 year showed significant improvement leading to their decannulation. Thus we would like to publish our results with scope of further research of this technique in this area and the treatment of such conditions affecting upper airway., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2021.)
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- 2022
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38. Clinical and Current Microbiological Profile with Changing Antibiotic Sensitivity in Malignant Otitis Externa.
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Sekar R, Raja K, Ganesan S, Alexander A, and Saxena SK
- Abstract
Malignant otitis externa (MOE) is a rare and fatal condition affecting temporal bone. It is also known as skull base osteomyelitis and is a rapidly progressive condition. This retrospective study evaluates the clinical, haematological, microbiological profile and management of malignant otitis externa in a tertiary care hospital and literature review. A retrospective review of 79 patients diagnosed with Malignant Otitis Externa from January 2015 to June 2021 was analyzed. History and Clinical findings, Imaging, Bacteriology, Random blood sugar on admission, Erythrocyte Sedimentation rate, HbA1C level, Biopsy of the granulation tissue from Externa auditory canal, cranial nerve involvement, duration of hospital stay, and treatment outcomes were analyzed. Out of 79 patients, otorrhea, otalgia, EAC oedema, and granulation were the most common findings. Facial nerve paralysis was found in 20 patients (25.3%) and multiple cranial nerve paralysis in 5 patients (6.3%). Uncontrolled diabetes mellitus and older age have increased duration of hospital stay, while cranial nerve paralysis did not affect this duration. Six different microorganisms were isolated. Pseudomonas aeruginosa was the most common organism cultured. Ciprofloxacin resistance was detected in 79% of cases. Amikacin, Cefaperazone-Sulbactam, and Piperacillin were the most sensitive antibiotics for gram negative organisms in our study. This study reviews the current microbiological profile and shows the need for higher-end antibiotics to treat MOE in present times. Early diagnosis, aggressive control of diabetes mellitus, and long duration culture-sensitive antibiotic therapy with regular monitoring are essential to reducing morbidity and mortality due to MOE., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest to disclose., (© Association of Otolaryngologists of India 2022.)
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- 2022
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39. A rare cause of recurrent pneumonia in an 8-year-old boy.
- Author
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Maya M, Raj D, Chandrasekaran V, Biswal N, Malla A, Govindarajan K, Gunasekaran V, Govindarajulu R, Sekar R, and Raja K
- Subjects
- Male, Humans, Child, Tomography, X-Ray Computed, Pneumonia diagnosis, Pneumonia etiology
- Published
- 2022
- Full Text
- View/download PDF
40. Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes.
- Author
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Sekar R, Motzler K, Kwon Y, Novikoff A, Jülg J, Najafi B, Wang S, Warnke AL, Seitz S, Hass D, Gancheva S, Kahl S, Yang B, Finan B, Schwarz K, Okun JG, Roden M, Blüher M, Müller TD, Krahmer N, Behrends C, Plettenburg O, Miaczynska M, Herzig S, and Zeigerer A
- Subjects
- Animals, Mice, Endosomes metabolism, Glucagon metabolism, Glucose metabolism, Lipids, Liver metabolism, Mammals metabolism, Mice, Inbred C57BL, Endosomal Sorting Complexes Required for Transport metabolism, Diabetes Mellitus, Type 2 metabolism, Receptors, Glucagon metabolism
- Abstract
During mammalian energy homeostasis, the glucagon receptor (Gcgr) plays a key role in regulating both glucose and lipid metabolisms. However, the mechanisms by which these distinct signaling arms are differentially regulated remain poorly understood. Using a Cy5-glucagon agonist, we show that the endosomal protein Vps37a uncouples glucose production from lipid usage downstream of Gcgr signaling by altering intracellular receptor localization. Hepatocyte-specific knockdown of Vps37a causes an accumulation of Gcgr in endosomes, resulting in overactivation of the cAMP/PKA/p-Creb signaling pathway to gluconeogenesis without affecting β-oxidation. Shifting the receptor back to the plasma membrane rescues the differential signaling and highlights the importance of the spatiotemporal localization of Gcgr for its metabolic effects. Importantly, since Vps37a knockdown in animals fed with a high-fat diet leads to hyperglycemia, although its overexpression reduces blood glucose levels, these data reveal a contribution of endosomal signaling to metabolic diseases that could be exploited for treatments of type 2 diabetes., Competing Interests: Declaration of interests B.F. and B.Y. are employees of Novo Nordisk., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
41. Stagnation trigger changes to tap water quality in winter season: Novel insights into bacterial community activity and composition.
- Author
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Zhang H, Liu X, Huang T, Ma B, Sun W, Zhao K, Sekar R, and Xing Y
- Subjects
- Adenosine Triphosphate, Bacteria, RNA, Ribosomal, 16S genetics, Seasons, Water Microbiology, Water Supply, Drinking Water, Water Quality
- Abstract
The drinking water distribution system is important for water supply and it affects the quality of the drinking water. Indoor pipeline water quality is regulated by physical, hydraulic and biological elements, such as indoor temperature and stagnation. In this work, the effects of indoor heating and overnight stagnation on the variation in bacterial community structure and the total cell count were assessed by full-length 16S rRNA gene sequencing and flow cytometry, respectively. The results exhibited that the average intact cell count was 6.99 × 10
4 cells/mL and the low nucleic acid (LNA) bacteria was 4.48 × 104 cells/mL after stagnation. The average concentration of total and intracellular adenosine triphosphate (ATP) was 3.64 × 10-12 gATP/mL and 3.13 × 10-17 gATP/cell in stagnant water, respectively. The growth of LNA cells played a crucial role in increasing ATP. The dominant phylum observed was Proteobacteria (87.21 %), followed by Actinobacteria (8.25 %). Opportunistic pathogens increased the risk of disease in stagnant water (up to 1.2-fold for Pseudomonas sp. and 5.8-fold for Mycobacterium sp.). Meanwhile, structural equation model (SEM) and redundancy analysis (RDA) also illustrated that water temperature, residual chlorine and Fe significantly affected the abundance and composition of bacterial community. Taking together, these results show response of tap water quality to overnight stagnation and indoor heating, and provide scientific basis for drinking water security management in winter season., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
42. Late termination of pregnancy at a major Queensland tertiary hospital, 2010-2020.
- Author
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Rosser S, Sekar R, Laporte J, Duncombe GJ, Bendall A, Lehner C, Portmann C, McGrath P, Lust K, Ganter P, and Kumar S
- Subjects
- Pregnancy, Female, Humans, Infant, Retrospective Studies, Tertiary Care Centers, Queensland, Pregnancy Trimester, Third, Gestational Age, Abortion, Induced methods
- Abstract
Objective: To review rates of and indications for late pregnancy feticide at a major Queensland tertiary perinatal centre over the past decade., Design: Retrospective cohort study., Setting, Participants: The Centre for Advanced Prenatal Care at the Royal Brisbane and Women's Hospital, a tertiary perinatal centre; feticides of singleton pregnancies of at least 22 weeks' gestation, 1 January 2010 - 31 December 2020., Main Outcome Measures: Indications for feticide; median gestational age at feticide; referral source; time between referral, maternal-fetal medicine review, and feticide., Results: During 2010-2020, 305 feticides were undertaken at 22 weeks' gestation or later. The annual number of feticides increased from 20 in 2010 to 54 in 2020. The median gestational age at feticide was consistent across the decade (24
+6 weeks; range, 17+0 to 37+1 weeks). The most frequent fetal indications for feticide were neurological abnormalities (110 of 305, 36%), aneuploidy or genetic syndromes (67, 22%), and cardiac malformations (59, 19%). Most women were seen for review within seven days of referral for feticide (154 of 197 for whom this information was available, 78%; median, five days; range, 0-34 days), and 136 of 197 feticides (69%) were undertaken within seven days of the initial maternal-fetal medicine review., Conclusions: Most late pregnancy feticides were performed because of fetal indications, primarily structural malformations or genetic abnormalities. Despite advances in prenatal imaging and diagnosis, late termination of pregnancy remains a necessary option in some pregnancies with maternal or fetal indications, and equitable access to late termination of pregnancy services is a vital component of reproductive health care., (© 2022 AMPCo Pty Ltd.)- Published
- 2022
- Full Text
- View/download PDF
43. Diversity and abundance of antibiotic resistance genes and their relationship with nutrients and land use of the inflow rivers of Taihu Lake.
- Author
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Fernanda PA, Liu S, Yuan T, Ramalingam B, Lu J, and Sekar R
- Abstract
Taihu Lake is the third largest freshwater lake in China and an important source for drinking water, flood protection, aquaculture, agriculture, and other activities. This lake is connected to many principal and small rivers with inflow from west and outflow on the eastern side of the lake and these inflow rivers are believed to significantly contribute to the water pollution of the lake. This study was aimed at assessing the diversity and abundance of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), and their relationship with water quality parameters and land use patterns. Water samples were collected from 10 major inflow rivers and the source water protection area of the Taihu Lake in spring and summer 2019. High-throughput profiling was used to detect and quantify 384 ARGs and MGEs and in addition, 11 water quality parameters were analyzed. The results showed that the number of ARGs/MGEs detected in each inflow river ranged from 105 to 185 in spring and 107 to 180 in summer. The aminoglycoside resistance genes were the most dominant types ARGs detected followed by beta-lactam resistance, multidrug resistance, macrolide-lincosamide-streptogramin B (MLSB) resistance genes, which contributed to 65% of the ARGs. The water quality parameters showed significant correlation with absolute abundance of ARGs. Furthermore, significant correlation between ARGs and MGEs were also observed which demonstrates potential gene transfer among organisms through horizontal gene transfer via MGEs. ARGs showed strong positive correlation with cultivated and industrial lands whereas, negative correlation was observed with river, lake, forest, land for green buffer, and land for port and harbor. The overall results indicate that the inflow rivers of Taihu Lake are polluted by various sources including multiple nutrients and high abundance of ARGs, which needs attention for better management of the inflow rivers of this lake., Competing Interests: Author BR was employed by Suzhou Xishan Biotechnology Inc. (VRL Asia). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fernanda, Liu, Yuan, Ramalingam, Lu and Sekar.)
- Published
- 2022
- Full Text
- View/download PDF
44. Single-centre survey of women reflecting on recent experiences and preferences of oral intake during labour.
- Author
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McDermott L, Pelecanos A, Krepska A, de Jersey S, Sekar R, Mao D, Lee G, Blackie A, and Eley V
- Subjects
- Adult, Female, Humans, Pregnancy, Pregnant Women, Surveys and Questionnaires, Cesarean Section, Labor, Obstetric
- Abstract
Background: Consensus-based recommendations guiding oral intake during labour are lacking., Aims: We surveyed women at a tertiary women's hospital about preferences for and experiences of oral intake during labour, gastrointestinal symptoms during labour and recalled advice about oral intake., Materials and Methods: Women who experienced labour completed a postpartum survey with responses as free text, yes-no questions and five-point Likert scales. We identified demographic data and risk factors for surgical or anaesthetic intervention at delivery from medical records. We summarised free text comments using conventional content analysis., Results: One hundred and forty-nine women completed the survey (47% response rate). Their mean (SD) age was 31 (four) years, birthing at median gestation of 39 weeks (interquartile range: 38-40). One hundred and twenty-two (83%) and 44 (30%) women strongly agreed or agreed they felt like drinking and eating respectively during labour. Ninety women (61%) reported nausea and 47 women (32%) reported vomiting in labour. Forty-one women (28%) did not receive advice on oral intake during labour. Maternal risk factors for surgical intervention were identified in 72 (48%) women and fetal risk factors in 27 (18%) women. Thirty-one women (21%) delivered by emergency caesarean section., Conclusion: Pregnant women received variable advice regarding oral intake during labour, from variable sources. Most women felt like drinking but not eating during labour. Guidelines on oral intake in labour may be beneficial to women, balancing the preferences of women with risks of surgical intervention., (© 2022 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)
- Published
- 2022
- Full Text
- View/download PDF
45. Recent Advances and Challenges in Light Conversion Phosphor Materials for Third-Generation Quantum-Dot-Sensitized Photovoltaics.
- Author
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Sekar R, Ravitchandiran A, and Angaiah S
- Abstract
Photovoltaic (PV) technologies have received tremendous attention for producing clean and renewable energy from the Sun. Third-generation quantum-dot-sensitized solar cells (QDSCs) present promising alternatives to conventional silicon solar cells due to their unique properties such as simplicity in fabrication, lower processing temperature, high flexibility, semitransparent nature, and a theoretical conversion efficiency of up to 44%. However, the light-harvesting QD materials used in these SCs allow for the absorption of a small portion (from 300 to 800 nm) of the solar spectrum due to their narrow band gap. The nonabsorption of UV and near-infrared (NIR) light limits the power conversion efficiency (PCE) of these SCs. Hence, a PV technique that efficiently uses the entire solar spectrum becomes essential. The incorporation of light conversion phosphor materials (LCs) in QDSCs is a promising technology to absorb the whole part of the solar spectrum and enhance the PCE of these SCs. This review presents an overview of the advantages and limitations of QDSCs, different types of lanthanide-based light conversion phosphor materials, their synthesis and light conversion mechanism, and their influence on QDSCs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)
- Published
- 2022
- Full Text
- View/download PDF
46. Recent Developments in Heteroatom/Metal-Doped Carbon Dot-Based Image-Guided Photodynamic Therapy for Cancer.
- Author
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Sekar R, Basavegowda N, Jena S, Jayakodi S, Elumalai P, Chaitanyakumar A, Somu P, and Baek KH
- Abstract
Carbon nanodots (CNDs) are advanced nanomaterials with a size of 2-10 nm and are considered zero-dimensional carbonaceous materials. CNDs have received great attention in the area of cancer theranostics. The majority of review articles have shown the improvement of CNDs for use in cancer therapy and bioimaging applications. However, there is a minimal number of consolidated studies on the currently developed doped CNDs that are used in various ways in cancer therapies. Hence, in this review, we discuss the current developments in different types of heteroatom elements/metal ion-doped CNDs along with their preparations, physicochemical and biological properties, multimodal-imaging, and emerging applications in image-guided photodynamic therapies for cancer.
- Published
- 2022
- Full Text
- View/download PDF
47. External Auditory Canal Cholesteatoma Involving the Vertical Segment of the Facial Nerve: A Rare Case Report.
- Author
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Sekar R, Chowdhary S, and Alexander A
- Abstract
External auditory canal cholesteatomas (EACC), are rare, more so when they affect the facial nerve in its vertical mastoid segment. EACC are known to possess bone eroding properties, causing a variety of complications, similar to the better-known attic cholesteatomas. We describe here the novel surgical management of a case of EACC, affecting only the vertical segment of the facial nerve, causing seventh nerve palsy at the time of presentation. A 46 year old male, complaining of right-sided otalgia and otorrhea, presented with grade IV facial palsy and associated mild conductive hearing loss. Clinical examination and radiological investigations suggested the diagnosis of an external auditory canal cholesteatoma. The patient underwent a trans-canal facial nerve decompression along with the cholesteatoma removal. Post-operatively, the patient showed marked clinical improvement with the facial palsy reverting to grade II. EACC involving only the vertical segment of the facial nerve can be approached via the trans-canal route, in contrast to the conventional postauricular approach, with a good clinical outcome. To the best of our knowledge, our case pertains to the only case of EACC with complications, managed by trans-canal facial nerve decompression., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest regarding the publication of this paper., (© Association of Otolaryngologists of India 2021.)
- Published
- 2022
- Full Text
- View/download PDF
48. A novel, cost-effective lens irrigation system for rigid endoscopes in transnasal endoscopic surgery.
- Author
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Sekar R and Hassan MF
- Subjects
- Cost-Benefit Analysis, Humans, Endoscopes, Endoscopy methods
- Abstract
Background: In transnasal endoscopic surgical procedures, the lens of the endoscope often becomes fogged or smeared with mucus or blood. The surgeon has to clean the lens and reintroduce the endoscope multiple times during the surgery, making it a tiring process., Methods: This paper describes an innovative lens irrigation system comprising a modified 16 Fr Foley catheter, a 20 cc or 50 cc syringe filled with warm normal saline (0.9 per cent), and a commercially available intravenous infusion set. The rigid endoscope is introduced into the catheter through the urine draining port. When the lens gets smudged with blood or mucus, the irrigating saline in the syringe is forced through the inflating port., Results: A clear vision was restored immediately on flushing the syringe. The system did not compromise the operative space or hinder manoeuvrability., Conclusion: This cost-effective, innovative lens irrigation system saves the time spent in cleaning the lens and enhances operational efficiency, especially in a low-income setting.
- Published
- 2022
- Full Text
- View/download PDF
49. MALAT 1 a modulator of PD-1/PD-L1 regulation in oral malignancies: An emerging target in cancer therapy.
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Jayaraman S, Sekar R, Veeraraghavan VP, Raj AT, and Patil S
- Subjects
- B7-H1 Antigen metabolism, Gene Expression Regulation, Neoplastic, Humans, Programmed Cell Death 1 Receptor, Mouth Neoplasms drug therapy, RNA, Long Noncoding
- Published
- 2022
- Full Text
- View/download PDF
50. Hepatocyte-specific activity of TSC22D4 triggers progressive NAFLD by impairing mitochondrial function.
- Author
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Wolff G, Sakurai M, Mhamane A, Troullinaki M, Maida A, Deligiannis IK, Yin K, Weber P, Morgenstern J, Wieder A, Kwon Y, Sekar R, Zeigerer A, Roden M, Blüher M, Volk N, Poth T, Hackert T, Wiedmann L, De Angelis Rigotti F, Rodriguez-Vita J, Fischer A, Mukthavaram R, Limphong P, Tachikawa K, Karmali P, Payne J, Chivukula P, Ekim-Üstünel B, Martinez-Jimenez CP, Szendrödi J, Nawroth P, and Herzig S
- Subjects
- Animals, Fibrosis, Hepatocytes metabolism, Humans, Lipids, Mice, Mice, Inbred C57BL, Mitochondria metabolism, Transcription Factors metabolism, Diabetes Mellitus, Type 2 metabolism, Insulin Resistance, Non-alcoholic Fatty Liver Disease metabolism
- Abstract
Objective: Fibrotic organ responses have recently been identified as long-term complications in diabetes. Indeed, insulin resistance and aberrant hepatic lipid accumulation represent driving features of progressive non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis and non-alcoholic steatohepatitis (NASH) to fibrosis. Effective pharmacological regimens to stop progressive liver disease are still lacking to-date., Methods: Based on our previous discovery of transforming growth factor beta-like stimulated clone (TSC)22D4 as a key driver of insulin resistance and glucose intolerance in obesity and type 2 diabetes, we generated a TSC22D4-hepatocyte specific knockout line (TSC22D4-HepaKO) and exposed mice to control or NASH diet models. Mechanistic insights were generated by metabolic phenotyping and single-nuclei RNA sequencing., Results: Hepatic TSC22D4 expression was significantly correlated with markers of liver disease progression and fibrosis in both murine and human livers. Indeed, hepatic TSC22D4 levels were elevated in human NASH patients as well as in several murine NASH models. Specific genetic deletion of TSC22D4 in hepatocytes led to reduced liver lipid accumulation, improvements in steatosis and inflammation scores and decreased apoptosis in mice fed a lipogenic MCD diet. Single-nuclei RNA sequencing revealed a distinct TSC22D4-dependent gene signature identifying an upregulation of mitochondrial-related processes in hepatocytes upon loss of TSC22D4. An enrichment of genes involved in the TCA cycle, mitochondrial organization, and triglyceride metabolism underscored the hepatocyte-protective phenotype and overall decreased liver damage as seen in mouse models of hepatocyte-selective TSC22D4 loss-of-function., Conclusions: Together, our data uncover a new connection between targeted depletion of TSC22D4 and intrinsic metabolic processes in progressive liver disease. Hepatocyte-specific reduction of TSC22D4 improves hepatic steatosis and promotes hepatocyte survival via mitochondrial-related mechanisms thus paving the way for targeted therapies., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
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