Publications by authors named "Anju Singh"

147 Publications

Unravelling the potency of triazole analogues for inhibiting α-synuclein fibrillogenesis and disaggregation.

Org Biomol Chem 2021 Feb;19(7):1589-1603

Drug Design and Synthesis Lab., Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India.

A series of triazole-based compounds was synthesized using a click chemistry approach and evaluated for the inhibition of α-synuclein (α-syn) fibrillogenesis and its disaggregation. Compounds Tr3, Tr7, Tr12, Tr15, and Tr16 exhibited good effect in inhibiting α-syn fibrillogenesis confirmed by Thioflavin-T assay and fluorescence microscopy and α-syn disaggregation confirmed by fluorescence microscopy. Molecular docking was used to understand the plausible mechanism of the test compounds for inhibiting the α-syn fibrillogenesis and to verify the in vitro results. Compounds Tr3, Tr7, Tr12, Tr15 and Tr16 showed good binding interactions with the essential amino acid residues of α-syn. The compounds which were found to be good inhibitors or disaggregators had no toxic effects on the SH-SY5Y cell line. These compounds have the potential to be developed as therapeutic interventions against synucleinopathies including Parkinson's disease and Lewy body dementia.
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http://dx.doi.org/10.1039/d0ob02226hDOI Listing
February 2021

Central serous chorioretinopathy secondary to solar retinopathy: an unusual presentation.

BMJ Case Rep 2021 Jan 28;14(1). Epub 2021 Jan 28.

Ophthalmology, All India Institute of Medical Sciences, Jodhpur, India.

Solar retinopathy (SR) results from unprotected solar eclipse viewing and also from gazing at the sun for a long duration. It has been known for a long that direct viewing of the sun causes visual disruption. Usually, there is a disruption of the inner segment-outer segment junction, but an association of central serous chorioretinopathy (CSCR) with SR is quite rare. We report a case of CSCR associated with solar eclipse viewing.
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http://dx.doi.org/10.1136/bcr-2020-240027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845700PMC
January 2021

Diagnostic performance of biomarkers in maternal sepsis: A prospective observational study.

Int J Gynaecol Obstet 2020 Dec 11. Epub 2020 Dec 11.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objectives: Maternal sepsis is a life-threatening condition. Biomarkers have been found to be useful in early detection of sepsis in the critical care setting. We aimed to determine the diagnostic performance of different biomarkers such as procalcitonin, C-reactive protein (CRP), absolute eosinophil count, and activated partial thromboplastin time (aPTT) in maternal sepsis.

Methods: A total of 35 patients were enrolled in this prospective observational study. Patients with suspected sepsis were evaluated for multi-organ dysfunction. The blood samples for testing of these biomarker levels were obtained at the time of enrollment in the study (day 1), and on day 3 and day 7. Trends of each marker were followed and correlated with the clinical picture.

Results: Of 35 enrolled patients, 30 completed the study. Among these, 18 had sepsis and 12 were designated as without sepsis. Sensitivities of procalcitonin, CRP, aPTT, and absolute eosinophil count were 83.33%, 77.78%, 55.56%, and 58.82% whereas their specificities were 66.67%, 75.0%, 100%, and 75%, respectively. Area under the curve was highest for procalcitonin (0.813) followed in decreasing order by CRP (0.778), aPTT (0.731), and eosinophil count (0.642), respectively.

Conclusion: Procalcitonin and CRP may be used as a valuable adjunct in the clinical stepwise approach for the prompt diagnosis of maternal sepsis.
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http://dx.doi.org/10.1002/ijgo.13525DOI Listing
December 2020

Quinoline carboxamide core moiety-based compounds inhibit P. falciparumfalcipain-2: Design, synthesis and antimalarial efficacy studies.

Bioorg Chem 2021 Mar 24;108:104514. Epub 2020 Nov 24.

Drug Design and Synthesis Lab., Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address:

Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity. We integrated molecular hybridization strategy with in-silico drug design to develop FP2 inhibitors. In-vitro results of FP2 inhibition by Qs17, Qs18, Qs20 and Qs21 were found to be in low micromolar range with IC 4.78, 7.37, 2.14 and 2.64 µM, respectively. Among the 25 synthesized compounds, four compounds showed significant antimalarial activities. These compounds also depicted morphological and food-vacuole abnormalities much better than that of E-64, an established FP2 inhibitor. Overall these aromatic substituted quinoline carboxamides can serve as promising leads for the development of novel antimalarial agents.
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http://dx.doi.org/10.1016/j.bioorg.2020.104514DOI Listing
March 2021

Evaluation of heat stress through delayed sowing on physicochemical and functional characteristics of grains, whole meals and flours of India wheat.

Food Chem 2021 May 27;344:128725. Epub 2020 Nov 27.

Division of Genetics, Indian Agricultural Research Institute, New Delhi 110012, India.

The physicochemical and functional characteristics of grain, meal and flour of timely sown wheat (TSW) and delayed sown wheat (DSW) were compared to see the effects of heat stress (HS). TSW and DSW of different lines were sown as per the approved timings. DSW experienced higher temperature during flowering and had shorter vegetative and maturation period than TSW. Pasting and dough rheological properties were measured using Rapid Visco-Analyser and Farinograph, respectively, while gliadins and glutenins profiling was done by SDS-PAGE. Delayed sowing decreased grain yield and diameter while increased protein and all categories of gliadins and high molecular weight glutenins. DSW showed higher peak viscosity, breakdown-viscosity and dough stability and lower setback viscosity, damaged starch, arabinoxylans and water absorption than TSW. HS in DSW appeared to lower starch synthesis causing proportionate increase in grain hardness and proteins content leading to changes in milling and rheological characteristics.
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http://dx.doi.org/10.1016/j.foodchem.2020.128725DOI Listing
May 2021

Clinical outcome of older adults with acute myeloid Leukemia: An analysis of a large tertiary referral Center over two decades.

J Geriatr Oncol 2020 Nov 19. Epub 2020 Nov 19.

Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Campus Virchow-Clinic, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Labor Berlin Charité Vivantes GmbH, Berlin, Germany.

Objective: In older adults with acute myeloid leukemia (AML), the overall outcome is still dismal and long-term data on survival are scarce, particularly outside of clinical trials. Here, we assess characteristics, prognostic factors and long-term survival in patients ≥60 years who were treated for AML at our center over the past 17 years.

Methods: 590 older adults with newly diagnosed AML were characterized according to Eastern Cooperative Oncology Group (ECOG) score, Charlson comorbidity index (CCI), European LeukemiaNet (ELN) risk, type of therapy, serum ferritin (SF) and further baseline characteristics. Survival analysis was performed accordingly.

Results: Median age was 68 years and most patients were in good general condition. Median follow-up was 55.8 months. Of all patients, 66% received intensive chemotherapy (IC) +/- allogeneic hematopoietic stem cell transplantation (allo-HSCT). The remaining cohort received palliative chemotherapy (PC, 26%) or best supportive care only (BSC, 8%). Enrollment rate for interventional clinical trials was 26%. 5-year overall survival (OS) and relapse-free survival (RFS) were 18% (median 12.5 months) and 11,5% (median 10.0 months). Long-term survival was independently influenced by ECOG score, ELN risk group, baseline SF, previous myocardial infarction, and choice of therapy, but not consistently by age or CCI. Considering therapeutic subgroups, the contribution of particular parameters in predicting OS was most compelling in IC patients, but less consistent with PC or BSC.

Conclusion: Our results provide thorough insights into prognostication within therapeutic subgroups and emphasize the need for more detailed prognostic algorithms and routine geriatric assessment in the treatment of older adults with AML.
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http://dx.doi.org/10.1016/j.jgo.2020.11.001DOI Listing
November 2020

DNA binding and antiradical potential of ethyl pyruvate: Key to the DNA radioprotection.

Chem Biol Interact 2020 Dec 7;332:109313. Epub 2020 Nov 7.

CBRN Protection and Decontamination Research Group, Division of CBRN Defence, Institute of Nuclear Medicine & Allied Sciences, Timarpur, Delhi, 110054, India. Electronic address:

DNA is the store house of all necessary hereditary information for growth of cells and tissues. Physiological functionality of DNA depends on its 3D helical structure and any distortion in a structure may lead to mutation and genomic instability that may translate into disease like cancer. In order to prevent DNA damage, an exogenous compound is required that can either scavenge the excess free radicals or enhance the structural integrity of DNA through binding. In the present study, the binding mechanism of ethyl pyruvate (EP) with DNA models using different spectroscopic techniques was investigated for their structural integrity. Besides, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays were performed to determine the antioxidant scavenging of EP. Plasmid DNA relaxation assay was performed to assess the radioprotection efficacy of EP in the plasmid DNA. Circular dichroism (CD) and UV-Vis absorbance spectroscopic data confirmed the conformation change in ctDNA upon binding with EP. The molecular docking visualized that EP stacks between the DNA bases with a glide score of -2.117 kcalmol while EP binds in the minor groove region of DNA with the glide score of -1.414 kcalmol . DPPH and FRAP data confirmed that EP scavenges significantly radicals at higher concentrations. In vitro radioprotection study in plasmid DNA pBR322 showed that EP retained the supercoiled form of plasmid DNA at 50 Gy radiation dose.
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http://dx.doi.org/10.1016/j.cbi.2020.109313DOI Listing
December 2020

Oral Health-Related Quality of Life in Children and Adolescents of Indian population.

J Pharm Bioallied Sci 2020 Aug 28;12(Suppl 1):S619-S622. Epub 2020 Aug 28.

Department of Periodontics, People's Dental Academy, Bhopal, Madhya Pradesh, India.

Background: Kids and teenagers are more prone to oral diseases. Poor oral health has a significant impact on oral well-being-associated quality of life. Thus, we performed an investigation to examine the outcome of oral health status on the quality of life of children and adolescents in Indian population, by using the Oral Health Impact Profile-14 (OHIP-14).

Materials And Methods: A total of 100 children, ranging between 1 and 19 years of age who attended Indian hospitals from November 2016 to October 2019, were included in the study. The DMFT Index (Decayed, Missing, and Filled Teeth) and OHIP-14 were used as data collection tools. Association of the total OHIP-14 score and seven subscales associated with it was evaluated using Spearman's correlations.

Results: The results showed statistically noteworthy association between the toothbrushing regularity, number of dental appointments, history of oral trauma, smoking, and subdomains of OHIP-14 ( < 0.05).

Conclusion: Dental and oral health of an individual has a great impact on their quality of life.
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http://dx.doi.org/10.4103/jpbs.JPBS_113_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595523PMC
August 2020

Rupture of Unscarred Uterus With Intestinal Prolapse From Vagina Following Criminal Abortion.

Cureus 2020 Sep 22;12(9):e10601. Epub 2020 Sep 22.

Obstetrics and Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigarh, IND.

A 21-year-old unmarried and primigravida female indulged in criminal abortion at 18 weeks of gestation with the help of a village midwife. Instrumentation was done, and it led to uterine perforation with prolapse of 200 cm of small bowel through vagina. She was managed with resection of 160 cm of necrotic small bowel, repair of the uterine defect, and end jejunostomy, which was anastomosed with distal ileum three months later. This case highlights the risks of illegal abortion and the primitive societal mindset that forces unmarried women to resort to such means.
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http://dx.doi.org/10.7759/cureus.10601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584304PMC
September 2020

NRF2 Activation Promotes Aggressive Lung Cancer and Associates with Poor Clinical Outcomes.

Clin Cancer Res 2021 Feb 19;27(3):877-888. Epub 2020 Oct 19.

Translational Oncology, Genentech Inc., South San Francisco, California.

Purpose: Stabilization of the transcription factor NRF2 through genomic alterations in and occurs in a quarter of patients with lung adenocarcinoma and a third of patients with lung squamous cell carcinoma. In lung adenocarcinoma, loss often co-occurs with loss and -activating alterations. Despite its prevalence, the impact of NRF2 activation on tumor progression and patient outcomes is not fully defined.

Experimental Design: We model NRF2 activation, loss, and activation using novel genetically engineered mouse models. Furthermore, we derive a NRF2 activation signature from human non-small cell lung tumors that we use to dissect how these genomic events impact outcomes and immune contexture of participants in the OAK and IMpower131 immunotherapy trials.

Results: Our data reveal roles for NRF2 activation in (i) promoting rapid-onset, multifocal intrabronchiolar carcinomas, leading to lethal pulmonary dysfunction, and (ii) decreasing elevated redox stress in -mutant, -null tumors. In patients with nonsquamous tumors, the NRF2 signature is negatively prognostic independently of loss. Patients with lung squamous cell carcinoma with low NRF2 signature survive longer when receiving anti-PD-L1 treatment.

Conclusions: Our modeling establishes NRF2 activation as a critical oncogenic driver, cooperating with loss and activation to promote aggressive lung adenocarcinoma. In patients, oncogenic events alter the tumor immune contexture, possibly having an impact on treatment responses. Importantly, patients with NRF2-activated nonsquamous or squamous tumors have poor prognosis and show limited response to anti-PD-L1 treatment.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1985DOI Listing
February 2021

Biochemical and functional attributes of raw and boiled potato flesh and peel powders for suitability in food applications.

J Food Sci Technol 2020 Nov 11;57(11):3955-3965. Epub 2020 Apr 11.

Division of Vegetable Science, ICAR-Indian Agricultural Research Institute, New Delhi, 110 012 India.

Four different potato cultivars, namely, Kufri Chipsona 1 and Kufri Frysona (processing purpose), Kufri Jyoti and Kufri Bahar (table purpose) were converted into flesh and peel powder (raw and after boiling) and studied for their respective biochemical and functional attributes to get an idea of possible dynamics of their utilization in different food formulation as bioadditives. The 16 variants of powder obtained retained less than 10% moisture content and demonstrated 'very good' to 'fair' flowability. Peel powders recorded a higher total mineral, fiber, phenolic contents and total antioxidant activity than the flesh powders which were significantly affected by boiling. Among raw and boiled flesh powders, highest reducing and total sugars were recorded for Kufri Bahar while least was observed in Kufri Chipsona 1. Colour coordinate showed that boiling imparts brightness to flesh powder while peel powder got darkened. Boiling of the tubers resulted in an increase in the resistant starch (~ 29% maximum) and flavour (~ 180% maximum) component. Peel exhibited a total glycoalkaloid content in the range of 0.75 (Kufri Frysona) to 1.7 mg/100 g (Kufri Bahar) that is well within the acceptable limits. Rheological study of the flesh powders revealed a reduction of about 11-18 °C in pasting temperature and about 87-90% in peak viscosity, setback, breakdown value and final viscosity upon boiling. This study revealed that the traditional processing method such as boiling can significantly modify the techno-functional characteristics of potato flesh and peel powders which can further govern their end use in various food formulations.
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http://dx.doi.org/10.1007/s13197-020-04424-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520487PMC
November 2020

Effect of growing conditions on proximate, mineral, amino acid, phenolic composition and antioxidant properties of wheatgrass from different wheat (Triticum aestivum L.) varieties.

Food Chem 2021 Mar 29;341(Pt 1):128201. Epub 2020 Sep 29.

Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi 110012, India.

Wheatgrass juice powder (WJP) from four wheat varieties grown using soil, coco-peat with nutrient solution (CNS) and water (soaked (8 h), germinated (36 h) and harvested on 10th day) were examined for proximate composition, mineral, amino acid, phenolic (free and bound) composition and antioxidant properties. The yield, ash and protein contents of WJP ranged between 4.88-7.87%, 5.18-15.93% and 38.75-50.17%, respectively. The total phenolic, flavonoid, chlorophyll content (TCC) and antioxidant activity varied from 12.02 to 17.44 mg GAE/g, 4.38-10.10 mg QE/g, 3.01-5.63 mg/g, and 13.54-17.33 μmol TE/g, respectively. HD-3086 grown using soil exhibited highest antioxidant properties, TCC and Mg content. WJP of C-306 grown using CNS had abundant essential amino acids (AAs). Phenolic acids (ferulic, syringic and sinapic acids) and flavonoids (catechin, rutin, vitexin and isovitexin) and minerals (K, P, Ca, Mg, Na and Fe) were predominant in WJP. The AAs and free phenolics were more in CNS and soil grown WJP, respectively.
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http://dx.doi.org/10.1016/j.foodchem.2020.128201DOI Listing
March 2021

Newborn pulse oximetry screening in the UK: a 2020 survey.

Lancet 2020 09 17;396(10255):881. Epub 2020 Sep 17.

Neonatal Unit, Birmingham Women's Hospital, Birmingham Women's and Children's National Health Service Foundation Trust, Birmingham B15 2TG, UK; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)31959-0DOI Listing
September 2020

Concurrent Targeting of Potential Cancer Stem Cells Regulating Pathways Sensitizes Lung Adenocarcinoma to Standard Chemotherapy.

Mol Cancer Ther 2020 10 26;19(10):2175-2185. Epub 2020 Aug 26.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Cancer stem cells (CSC) are highly resistant to conventional chemotherapeutic drugs. YAP1 and STAT3 are the two transcription factors that facilitate the therapeutic resistance and expansion of CSCs. The objective of this study was to understand the cross-talk between YAP1 and STAT3 activities and to determine the therapeutic efficacy of targeting dual CSC-regulating pathways (YAP1 and STAT3) combined with chemotherapy in lung adenocarcinoma. Here, we showed that YAP1 contributes to CSC regulation and enhances tumor formation while suppressing apoptosis. Mechanistically, YAP1 promotes phosphorylation of STAT3 by upregulating IL6. In lung adenocarcinoma clinical specimens, expression correlated with that of ( < 0.01). More importantly, YAP1 and phosphorylated STAT3 (pSTAT3) protein expressions were significantly correlated ( < 0.0001) in primary lung adenocarcinoma as determined by IHC. Immunoblotting of 13 lung adenocarcinoma patient-derived xenografts (PDX) showed that all YAP1-expressing PDXs also exhibited pSTAT3. Additional investigations revealed that chemotherapy resistance and malignant stemness were influenced by upregulating NANOG, OCT4, and SOX2, and the expression of these targets significantly attenuated by genetically and pharmacologically hindering the activities of YAP1 and STAT3 and Therapeutically, the dual inhibition of YAP1 and STAT3 elicits a long-lasting therapeutic response by limiting CSC expansion following chemotherapy in cell line xenograft and PDX models of lung adenocarcinoma. Collectively, these findings provide a conceptual framework to target the YAP1 and STAT3 pathways concurrently with systemic chemotherapy to improve the clinical management of lung adenocarcinoma, based on evidence that these two pathways expand CSC populations that mediate resistance to chemotherapy.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541748PMC
October 2020

Fifteen-minute consultation: Paediatric organ and tissue donation.

Arch Dis Child Educ Pract Ed 2020 Aug 26. Epub 2020 Aug 26.

Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.

This article explores ways in which paediatricians can help increase awareness and embed organ and tissue donation in the end-of-life care process. This can save patient lives on the organ transplant waiting list, many of whom currently die prematurely. The information benefits multidisciplinary staff including doctors, nurses and allied professionals to (1) recognise triggers for making referral to the specialist nurse for organ donation in order to make timely assessment for suitability for organ and/or tissue donation, (2) plan a multidisciplinary approach for families to make decisions for the gift of life and (3) help provide on-going support to families and staff.
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http://dx.doi.org/10.1136/archdischild-2019-318457DOI Listing
August 2020

Spectroscopic and molecular modelling study of binding mechanism of bovine serum albumin with phosmet.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jan 8;244:118803. Epub 2020 Aug 8.

CBRN Protection and Decontamination Research Group, Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, DRDO, Timarpur, Delhi 110054, India. Electronic address:

Phosmet exerts its neurotoxicity by inhibiting acetylcholinesterase that catalyzes the degradation of acetylcholine (a neurotransmitter). Serum proteins are known to influence the biodistribution of various endogenous and exogenous compounds. In the present study, the binding interactions of phosmet with bovine serum albumin (BSA) was investigated to determine the free concentration of phosmet for its neurotoxicity. The binding mechanism was studied using fluorescence, UV-Vis absorption spectroscopy, circular dichroism (CD), and molecular docking techniques. UV-Vis absorption data showed an increase in absorbance of BSA upon binding with phosmet with a slight red-shift in the peak around 280 nm. Intrinsic fluorescence of BSA was quenched in the presence of phosmet. The quenching was observed to be inversely correlated to the temperature that indicated the formation of ground state non-fluorescent complex (static quenching). Binding constant values and n values for the binding of phosmet with BSA at three different temperatures confirmed non-covalent binding interactions with a single set of equivalent binding sites. Thermodynamic parameters ∆G (-137.40 ± 3.58 kJ mol); ΔH (-16.33 ± 5.28 kJ mol) and ΔS(-469 ± 12.45 kJ mol) confirmed that the binding was spontaneous and non-covalent interactions like electrostatic, hydrogen bonding and van der Waals forces played an important role in the binding. The CD data indicated the conformational change in BSA upon binding with phosmet which resulted in a change in the melting temperature. Molecular docking presented the binding model for BSA-phosmet complex and displayed that non-covalent interactions played a significant role in the binding mechanism.
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http://dx.doi.org/10.1016/j.saa.2020.118803DOI Listing
January 2021

GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma.

Sci Signal 2020 08 18;13(645). Epub 2020 Aug 18.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Disruption of the KEAP1-NRF2 pathway results in the transactivation of NRF2 target genes, consequently inducing cell proliferation and other phenotypic changes in cancer cells. Here, we demonstrated that GULP1 was a KEAP1-binding protein that maintained actin cytoskeleton architecture and helped KEAP1 to sequester NRF2 in the cytoplasm. In urothelial carcinoma of the bladder (UCB), silencing of GULP1 facilitated the nuclear accumulation of NRF2, led to constitutive activation of NRF2 signaling, and conferred resistance to the platinum drug cisplatin. Knockdown of GULP1 in UCB cells promoted tumor cell proliferation in vitro and enhanced tumor growth in vivo. In primary UCB, GULP1 silencing was more prevalent in muscle-invasive UCB compared to nonmuscle-invasive UCB. GULP1 knockdown cells showed resistance to cisplatin treatment. In parallel with decreased expression, we observed increased expression of , , and other candidate antioxidant genes in cisplatin-resistant cells. Furthermore, low or no expression of was observed in most cisplatin nonresponder cases. Silencing of GULP1 was associated with GULP1 promoter hypermethylation in cell lines and primary tumors, and a high frequency of GULP1 promoter methylation was observed in multiple sets of primary clinical UCB samples. Together, our findings demonstrate that GULP1 is a KEAP1-binding protein that regulates KEAP1-NRF2 signaling in UCB and that promoter hypermethylation of GULP1 is a potential mechanism of GULP1 silencing.
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http://dx.doi.org/10.1126/scisignal.aba0443DOI Listing
August 2020

Comparative Evaluation of CephNinja for Android and NemoCeph for Computer for Cephalometric Analysis: A Study to Evaluate the Diagnostic Performance of CephNinja for Cephalometric Analysis.

J Int Soc Prev Community Dent 2020 May-Jun;10(3):286-291. Epub 2020 Jun 15.

Department of Conservative Dentistry and Endodontics, Buddha Institute of Dental Sciences & Hospital, Patna, Bihar, India.

Background: Since the introduction of digitization in cephalometrics, orthodontics has experienced a new horizon. Technological advancement is usually followed by comparisons between the methods.

Aims: The aim of this study was to compare values of cephalometric analysis performed by CephNinja and NemoCeph for Downs's analysis.

Settings And Design: This prospective study was conducted using 100 diagnostic digital lateral cephalograms taken from the same machine. The samples were collected by non-probability convenience sampling procedures.

Materials And Methods: The diagnostic images were cropped to standard lateral cephalogram film dimension; a scale image was placed on the top for calibration, numbered 1-100 for identification and was saved in Joint Photographic Experts Group (JPEG) format. A laptop with mouse-controlled cursor was used for NemoCeph and an android phone controlled with finger touch screen was used for CephNinja. Landmark identification for cephalometric analysis was carried out as demanded by the software.

Statistical Analysis Used: One-way analysis of variance (ANOVA) was used for comparison between the variables, and one-way ANOVA followed by test was carried out to check the level of significance using Statistical Package for the Social Sciences software program, version 11.0.

Results: The result showed that the difference of mean values obtained using the two software showed no statistical significance for 70% variables. -axis, incisor occlusal plane angle, and the upper incisor to A-Pog showed a statistically significant difference.

Conclusion: CephNinja presented a satisfactory result with NemoCeph, and can be used interchangeably with confidence.
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http://dx.doi.org/10.4103/jispcd.JISPCD_4_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402247PMC
June 2020

Comparative evaluation of occlusal pits and fissures morphology modification techniques before application of sealants: An study.

Indian J Dent Res 2020 Mar-Apr;31(2):247-251

Department of Dentistry, Sri Shankaracharya Institute of Medical Sciences, Bhilai, Durg, Chhattisgarh, India.

Background: Pits and Fissures are recognized as being highly susceptible to caries. Pit and fissure sealants are one of the best methods of preventing caries as it occludes the fissures and pits from the accumulation of plaque and cariogenic microflora. There are different methods of cleaning and preparing occlusal pits and fissures for preventing caries which helps in alleviating oral health status of paediatric population.

Aim: The aim of the present study was to evaluate and compare the microleakage of pit and fissure sealants after using five different preparation techniques, namely: A) Conventional technique using pumice prophylaxis, B) enameloplasty with round carbide bur, C) enameloplasty with fissurotomy bur, D) air polisher, and E) air abrasion.

Materials And Methods: The study was conducted on 50 caries-free premolars extracted for orthodontic purpose. These teeth were randomly assigned to five groups, 10 teeth in each for receiving fissure sealant after different surface preparation; thermocycling and sectioning of samples were performed and microleakage was assessed under a stereomicroscope after methylene blue dye immersion.

Results: The results of air abrasion groups were significantly superior with "0" microleakage when compared to all other groups followed by round bur, fissurotomy bur, air polisher and pumice prophylaxis.

Conclusion: To improve the marginal adaptation of the sealants, minimally invasive methods are the most favoured methods of occlusal preparation. This study promises to show positive results for fissure sealants which are likely to play an important role in caries prevention and techniques that are intended to protect caries susceptible surfaces.
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http://dx.doi.org/10.4103/ijdr.IJDR_956_19DOI Listing
May 2020

Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity.

Pathogens 2020 May 14;9(5). Epub 2020 May 14.

Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.

The targeting of immunogens/vaccines to specific immune cells is a promising approach for amplifying immune responses in the absence of exogenous adjuvants. However, the targeting approaches reported thus far require novel, labor-intensive reagents for each vaccine and have primarily been shown as proof-of-concept with isolated proteins and/or inactivated bacteria. We have engineered a plasmid-based, complement receptor-targeting platform that is readily applicable to live forms of multiple gram-negative bacteria, including, but not limited to, , , and . Using as a model, we find that targeted bacteria show increased binding and uptake by macrophages, which coincides with increased p38 and p65 phosphorylation. Mice vaccinated with targeted bacteria produce higher titers of specific antibody that recognizes a greater diversity of bacterial antigens. Following challenge with homologous or heterologous isolates, these mice exhibited less weight loss and/or accelerated weight recovery as compared to counterparts vaccinated with non-targeted immunogens. Collectively, these findings provide proof-of-concept for plasmid-based, complement receptor-targeting of live gram-negative bacteria.
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http://dx.doi.org/10.3390/pathogens9050375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281241PMC
May 2020

Circular economy potential of e-waste collectors, dismantlers, and recyclers of Maharashtra: a case study.

Environ Sci Pollut Res Int 2020 Jun 14;27(17):22081-22099. Epub 2020 Apr 14.

National Institute of Industrial Engineering, Mumbai, India.

The paper investigates the potential of circular economy of authorized e-waste collectors, dismantlers, and recyclers of Maharashtra. The study determines the drivers and barriers associated with e-waste collection in the region. Furthermore, it explores the handling techniques including dismantling, recycling, and scrap disposal. This is done through a case study of a recycling company based in Mumbai, Maharashtra. A questionnaire-based survey is used to study e-waste processing units. The qualitative analysis of the questionnaire shows that lack of awareness of environmental impact is the greatest constraint in the collection of e-waste and data security is the most crucial driver for enhancing the collection of e-waste. The case study reveals that the quantity and type of e-waste are more important than the distance between the processing unit and the collection point. It discloses that the primary factor for building trust between e-waste collectors and waste holders is data security.
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http://dx.doi.org/10.1007/s11356-020-08320-3DOI Listing
June 2020

Comparative evaluation of 2D miniplates and 3D miniplates fixation in mandibular angle fracture - A clinical study.

Indian J Dent Res 2020 Jan-Feb;31(1):134-137

Private Practitioner, Multispecialty Dental Clinic Patna, Bihar, India.

Introduction: Mandibular angle fracture is common in road traffic accidents. This study was conducted to compare 3D miniplate system with 2D plates for treatment of mandibular angle fractures.

Materials And Methods: The study was conducted on 120 patients with mandibular angle fracture of both genders. After selecting patients, patients were divided into 2 groups of 60 each. In group I, patients were treated with 3D, 2.0-mm titanium plates, and in group II, patients were treated with 2D, 2.0-mm titanium miniplate in mandibular angle fracture. Patients were evaluated regularly after 1, 3, and 6 months for outcome of treatment.

Results: In group I, males were 22 and females were 38. In group II, males were 40 and females were 20. Right angle fracture was seen in 32 patients in group I and 26 in group II. Left angle fracture was seen in 24 in group I and 28 in group II. Right angle and left parasymphysis fracture was seen in 3 in group I and 4 in group II. Left angle and right parasymphysis fracture was seen in 1 in group I and 2 in group II. [Table 3], [Graph 1] shows that in group I, after 1 month sensory deficit was present in 5 patients and in group II in 12 patients. After 3 months, there were no patients with sensory deficit in group I and 2 in group II. Preoperatively in group I, mouth opening was 24 mm and in group II patients was 25.80 mm, which increased to 31.20 mm in group I and 28.20 mm in group II at 1 month, 32 mm in group I and 30 mm in group II at 3 months, and 37.20 and 32.12 mm in groups I and II, respectively, at 6 months. The difference was significant (P < 0.05).

Conclusion: 3D miniplate system is reliable and effective treatment modality for mandibular angle fractures as compared with traditional 2D miniplates.[INLINE:1].
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http://dx.doi.org/10.4103/ijdr.IJDR_885_19DOI Listing
April 2020

Identification of Small Molecule Enhancers of Immunotherapy for Melanoma.

Sci Rep 2020 03 30;10(1):5688. Epub 2020 Mar 30.

Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, Maryland, USA.

Small molecule based targeted therapies for the treatment of metastatic melanoma hold promise but responses are often not durable, and tumors frequently relapse. Response to adoptive cell transfer (ACT)-based immunotherapy in melanoma patients are durable but patients develop resistance primarily due to loss of antigen expression. The combination of small molecules that sustain T cell effector function with ACT could lead to long lasting responses. Here, we have developed a novel co-culture cell-based high throughput assay system to identify compounds that could potentially synergize or enhance ACT-based immunotherapy of melanoma. A BRAF mutant melanoma cell line, SB-3123 which is resistant to Pmel-1-directed ACT due to low gp100 expression levels was used to develop a homogenous time resolve fluorescence (HTRF), screening assay. This high throughput screening assay quantitates IFNγ released upon recognition of the SB-3123 melanoma cells by Pmel-1 CD8 T-cells. A focused collection of approximately 500 small molecules targeting a broad range of cellular mechanisms was screened, and four active compounds that increased melanoma antigen expression leading to enhanced IFNγ production were identified and their in vitro activity was validated. These four compounds may provide a basis for enhanced immune recognition and design of novel therapeutic approaches for patients with BRAF mutant melanoma resistant to ACT due to antigen downregulation.
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http://dx.doi.org/10.1038/s41598-020-62369-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105471PMC
March 2020

Incidence of postoperative flare-ups after single-visit and multiple-visit endodontic therapy in permanent teeth.

J Indian Soc Pedod Prev Dent 2020 Jan-Mar;38(1):79-83

Private Practice, Department of Oral Medicine and Radiology, Patna, Bihar, India.

Aim: Single- and multiple-visit root canal treatment has been the subject of long-standing debate in the endodontic community, so the purpose of this study was to determine the incidence of postoperative flare-up after single- and multiple-visit endodontic therapy in permanent teeth.

Materials And Methods: A total of 65 children aged >10 years who underwent root canal treatment were randomly categorized equally into two treatment groups: the first group underwent single-visit treatment, and the other group underwent multiple-visit therapy. The visual analog scale was employed to evaluate pain preoperatively and postoperatively after obturation. Recall visits were carried out after 1 week, 1 and 3, 6 and 9 months. The Statistical Package for the Social Sciences version 15.0 was employed for statistical analysis.

Results: Except at the baseline, at all the other time intervals, the mean pain score in the multiple-visit group was higher as compared to that of the single-visit group; statistically no significant difference was found.

Conclusion: The mean pain score in the single-visit group was lower as compared to that of the multiple-visit group; however, the difference between the two groups was statistically significant (P > 0.05).
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http://dx.doi.org/10.4103/JISPPD.JISPPD_354_19DOI Listing
March 2020

Factors impacting referral of JIA patients to a tertiary level pediatric rheumatology center in North India: a retrospective cohort study.

Pediatr Rheumatol Online J 2020 Mar 4;18(1):21. Epub 2020 Mar 4.

Division of Pediatric Rheumatology, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India.

Background: JIA studies demonstrate that there is a "window of opportunity" early in the disease course during which appropriate management improves outcomes. No data is available regarding patients' pathway, before first pediatric rheumatology (PR) evaluation in India, a country where health-care costs are self- paid by patients and where a significant shortage of pediatric rheumatologists (PRsts) is known. This study aimed to describe time from onset of symptoms to first PR visit of JIA patients to a tertiary center in India and factors that impact this.

Methods: This retrospective study is from data collected at the PR center, Sir Ganga Ram Hospital (SGRH) in New Delhi. JIA patients fulfilling ILAR 2004 criteria and seen at least twice from 1st October 2013 to 30th September 2018 were included. Data collected were: demographic details, history of disease, referral practitioner, clinical and laboratory features, treatments. Mann-Whitney U-test, Chi square and logistic regression were used as appropriate to study factors that determined time to first PR visit.

Results: Five hundred and twenty patients were included: 396 were diagnosed at this PR center (group A), 124 were previously diagnosed as JIA and managed by non PRsts before first PR visit (group B). Median time from symptom onset to first PR visit was 4.1 months and median distance travelled 119.5 km. Despite ongoing treatment, group B patients had more aggressive disease and resided further away as compared to Group A patients. On univariate analysis, factors that predicted PR visit within 3 months were private patients, short distance to travel, family history of inflammatory disease, history of fever, history of acute uveitis or high ESR. On multivariate analysis all these factors were significant except high ESR and acute uveitis.

Conclusion: Time to first PR assessment at this center was comparable to that seen in western countries. Cost of care and long distance to the center delayed consultation; acuity of complaints and family history of rheumatologic condition hastened referral. Possible solutions to improve referral to PR centers would be to increase the number of PRsts and to improve medical insurance coverage.
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http://dx.doi.org/10.1186/s12969-020-0408-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057446PMC
March 2020

Anxiolytic Drug FGIN-1-27 Ameliorates Autoimmunity by Metabolic Reprogramming of Pathogenic Th17 Cells.

Sci Rep 2020 02 28;10(1):3766. Epub 2020 Feb 28.

Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.

Th17 cells are critical drivers of autoimmune diseases and immunopathology. There is an unmet need to develop therapies targeting pathogenic Th17 cells for the treatment of autoimmune disorders. Here, we report that anxiolytic FGIN-1-27 inhibits differentiation and pathogenicity of Th17 cells in vitro and in vivo using the experimental autoimmune encephalomyelitis (EAE) model of Th17 cell-driven pathology. Remarkably, we found that the effects of FGIN-1-27 were independent of translocator protein (TSPO), the reported target for this small molecule, and instead were driven by a metabolic switch in Th17 cells that led to the induction of the amino acid starvation response and altered cellular fatty acid composition. Our findings suggest that the small molecule FGIN-1-27 can be re-purposed to relieve autoimmunity by metabolic reprogramming of pathogenic Th17 cells.
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http://dx.doi.org/10.1038/s41598-020-60610-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048748PMC
February 2020

NRF2, p53, and p16: Predictive biomarkers to stratify human papillomavirus associated head and neck cancer patients for de-escalation of cancer therapy.

Crit Rev Oncol Hematol 2020 Apr 1;148:102885. Epub 2020 Feb 1.

Centre of Excellence in Molecular Biology & Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, India. Electronic address:

Patients with HPV associated (HPV) head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal cancer, show better treatment response, higher survival rates, and lower risks of recurrence as compared to HPV HNSCC patients. Despite increased sensitivity to treatment modality, HPV HNSCC patients are subjected to the same intensive anti-cancer therapy as HPV HNSCC patients and thus subjecting them to unwarranted long-term toxicity. To identify predictive biomarkers for risk-stratification, we have analyzed the mutational spectrum, and the evidence suggests that gain-of-function mutations in the NRF2 pathway are highly prevalent in HPV HNSCC. At the same time, it is rare in HPV HNSCC tumors. We have reviewed the importance of gain-of-NRF2 function and loss of p53 in the prognosis of HNSCC patients and discussed a predictive scoring system using a combination of HPV status (p16), NRF2 pathway and p53 to stratify HPV HNSCC into good versus poor responders, which could immensely help in guiding future de-escalation treatment approaches in patients with HPV HNSCC.
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http://dx.doi.org/10.1016/j.critrevonc.2020.102885DOI Listing
April 2020

Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses.

Sci Transl Med 2020 02;12(530)

Rare Tumor Initiative, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this immune response is co-opted into contributing toward tumor growth instead of preventing its progression. We seek to reestablish an antitumor immune response by selectively targeting surface receptors and endogenous signaling processes of the macrophage subtypes driving cancer progression. RP-182 is a synthetic 10-mer amphipathic analog of host defense peptides that selectively induces a conformational switch of the mannose receptor CD206 expressed on TAMs displaying an M2-like phenotype. RP-182-mediated activation of this receptor in human and murine M2-like macrophages elicits a program of endocytosis, phagosome-lysosome formation, and autophagy and reprograms M2-like TAMs to an antitumor M1-like phenotype. In syngeneic and autochthonous murine cancer models, RP-182 suppressed tumor growth, extended survival, and was an effective combination partner with chemo- or immune checkpoint therapy. Antitumor activity of RP-182 was also observed in CD206 patient-derived xenotransplantation models. Mechanistically, via selective reduction of immunosuppressive M2-like TAMs, RP-182 improved adaptive and innate antitumor immune responses, including increased cancer cell phagocytosis by reprogrammed TAMs.
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http://dx.doi.org/10.1126/scitranslmed.aax6337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832040PMC
February 2020

An Uncommon Cause of Postmenopausal Bleeding.

J Midlife Health 2019 Oct-Dec;10(4):213-215

Department of Pathology, Government Medical College and Hospital, Chandigarh, India.

A 65-year-old multiparous female was evaluated for postmenopausal bleeding. Imaging was strongly suggestive of malignancy. However, hysteroscopic-guided endometrial biopsy revealed tuberculous endometritis. The patient responded to antitubercular therapy and recovered completely. Genital tuberculosis is typically considered a disease of young women presenting with infertility. However, tuberculous endometritis should be considered in a patient of postmenopausal bleeding, particularly in developing countries. It is a rare, but curable cause of postmenopausal bleeding.
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http://dx.doi.org/10.4103/jmh.JMH_17_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947718PMC
January 2020