Publications by authors named "Priti Kumari"

31 Publications

OncoTree: A Cancer Classification System for Precision Oncology.

JCO Clin Cancer Inform 2021 Feb;5:221-230

Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: Cancer classification is foundational for patient care and oncology research. Systems such as International Classification of Diseases for Oncology (ICD-O), Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT), and National Cancer Institute Thesaurus (NCIt) provide large sets of cancer classification terminologies but they lack a dynamic modernized cancer classification platform that addresses the fast-evolving needs in clinical reporting of genomic sequencing results and associated oncology research.

Methods: To meet these needs, we have developed OncoTree, an open-source cancer classification system. It is maintained by a cross-institutional committee of oncologists, pathologists, scientists, and engineers, accessible via an open-source Web user interface and an application programming interface.

Results: OncoTree currently includes 868 tumor types across 32 organ sites. OncoTree has been adopted as the tumor classification system for American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE), a large genomic and clinical data-sharing consortium, and for clinical molecular testing efforts at Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute. It is also used by precision oncology tools such as OncoKB and cBioPortal for Cancer Genomics.

Conclusion: OncoTree is a dynamic and flexible community-driven cancer classification platform encompassing rare and common cancers that provides clinically relevant and appropriately granular cancer classification for clinical decision support systems and oncology research.
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http://dx.doi.org/10.1200/CCI.20.00108DOI Listing
February 2021

SARS-CoV-2 and the reproductive system: known and the unknown..!!

Middle East Fertil Soc J 2021 7;26(1). Epub 2021 Jan 7.

Department of Obstetrics & Gynecology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012 India.

Background: COVID-19 is the most recent zoonotic outbreak of coronaviruses. Mostly, it invades the cells of the respiratory system by binding to the receptor angiotensin-converting enzyme 2 (ACE2) which is also present in other organs like the kidney, testis, ovaries, breast, heart, and intestine, rendering them prone to be infected. The reproductive potential is a must for the sustenance of any species and it is our prime duty to safeguard the reproductive system of the present generation from such a deadly virus. The previously reported coronaviruses like severe acute respiratory syndrome coronavirus (SARS-CoV) had a detrimental impact on reproductive organs. There is a dearth of sufficient research to provide substantial evidence for the harmful effects of this novel virus on the reproductive system. Hence, our review compiles the knowledge available until now to boost research in this regard and to take the necessary steps in time.

Main Body Of Abstract: Here we tried to compile all the data available on the effect of SARS-CoV-2 on the reproductive system as well as vertical transmission of the virus. All related articles published from February to August 2020 were reviewed and thoroughly analyzed. SARS-CoV-2 has been found to affect the sperm concentration and motility, thus degrading the fertility of males. In females, it is suspected that this virus affects the oocyte quality and ovarian function, resulting in infertility or miscarriage. Traces of SARS-CoV-2 virus have also been found in the breast milk of the infected mothers and the semen of infected males. Vertical transmission of SARS-CoV-2 has also been reported in some cases.

Conclusion: Based on the literature review, SARS-CoV-2 seems to have the potential of affecting both male and female reproductive tracts. This review brings together the findings and observations made in the area of reproductive health during the current pandemic. The reproductive system of the young population is preordained for subsequent disorders, infertility, reduced sperm count, and motility. Therefore, the research and medical practices should focus on possible vulnerability being posed by SARS-CoV-2 to the gametes and future generations. We, hereby, recommend close monitoring of young and pregnant COVID-19 patients concerning reproductive health with utmost priority.
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http://dx.doi.org/10.1186/s43043-020-00046-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789900PMC
January 2021

Tube Shunt Revision with Excision of Fibrotic Capsule Using Mitomycin C with and without Ologen-a Collagen Matrix Implant: A 3-Year Follow-up Study.

J Glaucoma 2020 Dec 29;Publish Ahead of Print. Epub 2020 Dec 29.

Glaucoma services, Dr. Shroff charity eye hospital, Daryaganj, New Delhi-110092, India Department, Glaucoma services, Dr. Shroff charity eye hospital, Daryaganj, New Delhi-110092, India.

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http://dx.doi.org/10.1097/IJG.0000000000001778DOI Listing
December 2020

Genomic Characterization of Metastatic Breast Cancer.

Clin Cancer Res 2021 Feb 8;27(4):1105-1118. Epub 2020 Dec 8.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Purpose: In contrast to recurrence after initial diagnosis of stage I-III breast cancer [recurrent metastatic breast cancer (rMBC)], metastatic breast cancer (dnMBC) represents a unique setting to elucidate metastatic drivers in the absence of treatment selection. We present the genomic landscape of dnMBC and association with overall survival (OS).

Experimental Design: Targeted DNA sequencing (OncoPanel) was prospectively performed on either primary or metastatic tumors from 926 patients (212 dnMBC and 714 rMBC). Single-nucleotide variants, copy-number variations, and tumor mutational burden (TMB) in treatment-naïve dnMBC primary tumors were compared with primary tumors in patients who ultimately developed rMBC, and correlated with OS across all dnMBC.

Results: When comparing primary tumors by subtype, amplification was enriched in triple-negative dnMBC versus rMBC (21.1% vs. 0%, = 0.0005, = 0.111). Mutations in , and were more prevalent, and and less prevalent, in primary HR/HER2 tumors of dnMBC versus rMBC, though not significant after multiple comparison adjustment. Alterations associated with shorter OS in dnMBC included TP53 (wild-type: 79.7 months; altered: 44.2 months; = 0.008, = 0.107), MYC (79.7 vs. 23.3 months; = 0.0003, = 0.011), and cell-cycle (122.7 vs. 54.9 months; = 0.034, = 0.245) pathway genes. High TMB correlated with better OS in triple-negative dnMBC ( = 0.041).

Conclusions: Genomic differences between treatment-naïve dnMBC and primary tumors of patients who developed rMBC may provide insight into mechanisms underlying metastatic potential and differential therapeutic sensitivity in dnMBC. Alterations associated with poor OS in dnMBC highlight the need for novel approaches to overcome potential intrinsic resistance to current treatments.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887078PMC
February 2021

Fetal Ovarian Cyst Managed Laparoscopically in the Neonatal Period.

Indian Pediatr 2020 09;57(9):866-867

Department of Pediatric Surgery, Maulana Azad Medical Collage and Lok Nayak Hospital, New Delhi, India.

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September 2020

Identifying Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials.

JCO Precis Oncol 2019 15;3. Epub 2019 Nov 15.

Dana-Farber Cancer Institute, Boston, MA.

Purpose: The yield of comprehensive genomic profiling in recruiting patients to molecular-based trials designed for small subgroups has not been fully evaluated. We evaluated the likelihood of enrollment in a clinical trial that required the identification of a specific genomic change based on our institute-wide genomic tumor profiling.

Patients And Methods: Using genomic profiling from archived tissue samples derived from patients with metastatic breast cancer treated between 2011 and 2017, we assessed the impact of systematic genomic characterization on enrollment in an ongoing phase II trial (ClinicalTrials.gov identifier: NCT01670877). Our primary aim was to describe the proportion of patients with a qualifying mutation identified by our institutional genomic panel (OncoMap or OncoPanel) who enrolled in the trial. Secondary objectives included median time from testing result to trial registration, description of the spectrum of mutations, and survival. Associations were calculated using Fisher's exact test.

Results: We identified a total of 1,045 patients with metastatic breast cancer without amplification who had available genomic testing results. Of these, 42 patients were found to have mutation and 19 patients (1.8%) were eligible for the trial on the basis of the presence of an activating mutation, 18 of which were identified by OncoPanel testing. Fifty-eight percent of potentially eligible patients were approached, and 33.3% of eligible patients enrolled in the trial guided exclusively by OncoPanel testing.

Conclusion: More than one half of eligible patients were approached for trial participation and, significantly, one third of those were enrolled in NCT01670877. Our data illustrate the ability to enroll patients in trials of rare subsets in routine clinical practice and highlight the need for these broadly based approaches to effectively support the success of these studies.
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http://dx.doi.org/10.1200/PO.19.00087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446367PMC
November 2019

Effects of Intravitreal Anti-VEGF Therapy on Glaucoma-like Progression in Susceptible Eyes.

J Glaucoma 2020 10;29(10):e120

Glaucoma Services, Dr Shroff Charity Eye Hospital, Daryaganj, New Delhi, India.

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http://dx.doi.org/10.1097/IJG.0000000000001618DOI Listing
October 2020

Publisher Correction: Design and efficient synthesis of pyrazoline and isoxazole bridged indole C-glycoside hybrids as potential anticancer agents.

Sci Rep 2020 Jun 17;10(1):10095. Epub 2020 Jun 17.

Department of Chemistry, School of Natural Sciences, Shiv Nadar University (SNU), NH91, Tehsil-Dadri, Gautam Buddha Nagar, Uttar Pradesh, 201314, India.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-67068-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298019PMC
June 2020

Design and efficient synthesis of pyrazoline and isoxazole bridged indole C-glycoside hybrids as potential anticancer agents.

Sci Rep 2020 04 20;10(1):6660. Epub 2020 Apr 20.

Department of Chemistry, School of Natural Sciences, Shiv Nadar University (SNU), NH91, Tehsil-Dadri, Gautam Buddha Nagar, Uttar Pradesh, 201314, India.

C-glycosides are important class of molecules exhibit diverse biological activities and present as structural motif in many natural products. Two series of new pyrazoline and isoxazole bridged indole C-glycoside molecular hybrids (n = 36) were efficiently synthesized starting from diverse indole 3-carboxaldehydes derived α, β-unsaturated ketone derivatives of β-D-glucosyl-propan-2-one, β-D-galactosyl-propan-2-one and β-D-mannosyl-propan-2-one, reacting with hydrazine hydrate and hydroxyl amine hydrochloride in shorter reaction time (15 min) under microwave assisted condition. Anticancer activity of these newly synthesized pyrazoline and isoxazole bridged indoles C-glycoside hybrids were determined in details through cellular assays against MCF-7, MDA-MB-453 and MDA-MB-231 cancer cell lines. The selected library members displayed low micromolar (IC = 0.67-4.67 µM) and selective toxicity against breast cancer cell line (MCF-7). Whereas these compounds were nontoxic towards normal cell line (MCF-10A). Mechanistic studies showed that, active compounds inhibit COX-2 enzyme, which was also supported by molecular docking studies. These findings are expected to provide new leads towards anticancer drug discovery.
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http://dx.doi.org/10.1038/s41598-020-63377-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170901PMC
April 2020

Re-annotation of the Theileria parva genome refines 53% of the proteome and uncovers essential components of N-glycosylation, a conserved pathway in many organisms.

BMC Genomics 2020 Apr 3;21(1):279. Epub 2020 Apr 3.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Background: The apicomplexan parasite Theileria parva causes a livestock disease called East coast fever (ECF), with millions of animals at risk in sub-Saharan East and Southern Africa, the geographic distribution of T. parva. Over a million bovines die each year of ECF, with a tremendous economic burden to pastoralists in endemic countries. Comprehensive, accurate parasite genome annotation can facilitate the discovery of novel chemotherapeutic targets for disease treatment, as well as elucidate the biology of the parasite. However, genome annotation remains a significant challenge because of limitations in the quality and quantity of the data being used to inform the location and function of protein-coding genes and, when RNA data are used, the underlying biological complexity of the processes involved in gene expression. Here, we apply our recently published RNAseq dataset derived from the schizont life-cycle stage of T. parva to update structural and functional gene annotations across the entire nuclear genome.

Results: The re-annotation effort lead to evidence-supported updates in over half of all protein-coding sequence (CDS) predictions, including exon changes, gene merges and gene splitting, an increase in average CDS length of approximately 50 base pairs, and the identification of 128 new genes. Among the new genes identified were those involved in N-glycosylation, a process previously thought not to exist in this organism and a potentially new chemotherapeutic target pathway for treating ECF. Alternatively-spliced genes were identified, and antisense and multi-gene family transcription were extensively characterized.

Conclusions: The process of re-annotation led to novel insights into the organization and expression profiles of protein-coding sequences in this parasite, and uncovered a minimal N-glycosylation pathway that changes our current understanding of the evolution of this post-translational modification in apicomplexan parasites.
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http://dx.doi.org/10.1186/s12864-020-6683-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126163PMC
April 2020

Correction to: Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential.

Malar J 2020 03 24;19(1):122. Epub 2020 Mar 24.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.

Please note, following publication of the original article [1], the authors have advised of two errors that are present in the published article.
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http://dx.doi.org/10.1186/s12936-020-03179-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092511PMC
March 2020

Transulnar versus Transradial Access as a Default Strategy for Percutaneous Coronary Intervention.

Heart Views 2019 Oct-Dec;20(4):152-157. Epub 2019 Nov 14.

Department of Cardiology, JLN Medical College, Ajmer, Rajasthan, India.

Background: Percutaneous coronary interventions (PCI) are undergoing a paradigm shift from femoral to forearm approach due to obvious advantages in terms of patient safety, comfort, and faster ambulation. Transradial access (TRA) has been established as a primary forearm access site. Use of transulnar access (TUA) as an alternative to radial route can serve as novel forearm access to the interventionalists.

Aim: The aim of this study is to evaluate TUA versus TRA access as a default strategy for PCI.

Materials And Methods: This was a prospective, single-center randomized controlled trial involving 2700 patients, of whom 220 underwent PCI in 1:1 randomization to TUA ( = 110) or TRA ( = 110). The primary endpoint was composite of major adverse cardiac events during hospital stay, cross-over to another arterial site, major vascular events of the arm during hospital stay (large hematoma with hemoglobin drop of ≥5 g%) and occlusion rate. Secondary endpoints were individual components of primary endpoint and spasm of the vessel.

Results: Two groups did not differ in baseline characteristics. On intention to treat (ITT) analysis, primary end point occurred in 10.91% of TUA and 12.73% of TRA arm (odds ratio [OR]: 0.84; 95% confidence interval [CI], 0.37-1.91; = 0.68 at α = 0.05). Further on per protocol (PP) analysis, primary end point occurred in 9.21% of TUA and 11.11% of TRA arm (OR: 0.81; 95% CI, 0.29-2.30; = 0.68 at α = 0.05). Secondary endpoints also did not differ significantly between the two groups in ITT and PP analysis.

Conclusions: TUA is an excellent alternative to TRA, while performing PCI when performed by an experienced operator. When utilized as an option, TUA increases the chance of success with forearm access and reduces the need for cross over to femoral route.
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http://dx.doi.org/10.4103/HEARTVIEWS.HEARTVIEWS_96_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881864PMC
November 2019

Triazole Linked -Acetylglucosamine Based Gelators for Crude Oil Separation and Dye Removal.

Langmuir 2019 12 13;35(51):16803-16812. Epub 2019 Dec 13.

Department of Chemistry, School of Natural Sciences , Shiv Nadar University (SNU) , NH91, Tehsil-Dadri , Gautam Buddha Nagar, Uttar Pradesh 201314 , India.

Marine oil-spills have a long-lasting impact on the environment; therefore, it is a major concern in the scientific community to find a solution for remediation. Recently, phase selective organo-gelators emerged as potential materials for removal of oil from water through selective gelation. Herein, we report synthesis of a series of C-6 triazole linked -acetylglucosamine derivatives, among which three have shown excellent selective gelation of organic solvents, diesel, petrol, and crude oils in water and seawater. We have studied phase selective gelation against different API grade crude oils (from light to heavy), and the gelation was achieved using nontoxic carrier solvent at room temperature in less than 15 min, and gelators were found useful for recovering crude oils. Critical gel concentration (CGC) of crude oil gelators was found to be 2.3-12% (w/v). The variable temperature NMR and FTIR experiments reveal that intermolecular hydrogen bonding was responsible for gel formation. Furthermore, a gelator was utilized for selective dye removal from water.
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http://dx.doi.org/10.1021/acs.langmuir.9b02704DOI Listing
December 2019

Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential.

Malar J 2019 Oct 11;18(1):346. Epub 2019 Oct 11.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.

Background: Malaria is one of the deadliest infectious diseases caused by protozoan parasite of Plasmodium spp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates.

Methods: Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened against Plasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay on P. falciparum 3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid 12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid 12 by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid 12 treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid 12 on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay.

Results: 2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid 12 exhibited maximum growth inhibitory potential against Plasmodium with IC value of 5.861 µM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid 12 arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid 12 binds to α,β-heterodimer of tubulin and affects microtubule dynamics.

Conclusion: These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions against P. falciparum.
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http://dx.doi.org/10.1186/s12936-019-2971-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788091PMC
October 2019

Acute Fulminant Uremic Neuropathy Following Coronary Angiography Mimicking Guillain Barre Syndrome.

J Assoc Physicians India 2019 Aug;67(8):90-91

Assistant Professor, JLN Medical College, Ajmer, Rajasthan.

A 55 yr old diabetic lady suffered a posterior wall STEMI. She developed Contrast induced nephropathy following coronary angiography. Acute fulminant uremic neuropathy was precipitated which initially mimicked Guillan Barre Syndrome, hence reported.
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August 2019

Maternal and severe anaemia in delivering women is associated with risk of preterm and low birth weight: A cross sectional study from Jharkhand, India.

One Health 2019 Dec 19;8:100098. Epub 2019 Aug 19.

Research Laboratory, University Department of Zoology, Vinoba Bhave University, Hazaribag, Jharkhand, India.

Background And Objectives: Haemoglobin content is the well accepted indicator for anaemia assessment. The high prevalence of anaemia, maternal health care issues and adverse delivery outcome in Jharkhand, we investigated whether delivering women with anaemia would present a modifiable risk of preterm (PTB) and low birth weight (LBW).

Methods: A facility-based cross-sectional study involving pregnant women, with screening for pregnancy endpoints and haemoglobin assay, were conducted. Anaemia was classified according to World Health Organization's definition of anaemia in pregnancy. Confounding variables were adjusted in a logistic model. The adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were used for analyzing the association among maternal anaemia, PTB and LBW.

Results: We observed a high prevalence of anaemia (78.45%) in delivering women, whereas high prevalence of preterm birth (34.75%) and LBW (32.81%) in delivering women overall. In the adjusted analysis, overall anaemia in pregnancy was strongly associated with preterm birth (OR, 3.42; 95% CI, 1.98-5.88;   ) as compared to LBW (OR, 1.12; 95% CI, 0.65-1.61;   ). The risk of PTB and LBW were dependent on the stratification of the anaemia group, as the strongest association was observed in severe (OR, 4.86) followed by mild (OR, 3.66) and moderate (OR, 3.18) anaemia in PTB; whereas risk of LBW was found in severe (OR, 2.5) followed by moderate (OR, 1.11) and mild (OR, 0.57) anaemia. The risk of PTB and LBW across six pregnancy haemoglobin groups were compared, haemoglobin of 10-10.9 g/dl (OR, 1.25) and ≤ 8 g/dl (OR, 1.03) have shown association with PTB and LBW, respectively. However, high haemoglobin concentration was not associated with either PTB or LBW.

Conclusions: Anaemia in delivering women was associated with an elevated risk of PTB and LBW and the risk increased with the severity of anaemia in pregnant women.
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http://dx.doi.org/10.1016/j.onehlt.2019.100098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715890PMC
December 2019

Comparison of lower loading dose of prasugrel with conventional loading dose of prasugrel in Indian patients undergoing percutaneous coronary interventions.

Indian Heart J 2018 Dec 18;70 Suppl 3:S319-S322. Epub 2018 Aug 18.

Department of Cardiology, JLN Medical College, Ajmer, Rajasthan, India.

Background: Although conventional 60 mg of prasugrel allows for rapid and potent platelet inhibition within 30 min after loading dose, the efficacy and safety of lower doses of prasugrel in Indian patients has not yet been investigated.

Objective: The study sought to compare the efficacy of a lower loading dose of prasugrel with conventional loading dose of prasugrel in Indian patients.

Material And Methods: Three hundred thirty-two Indian patients undergoing elective percutaneous coronary intervention (PCI) were enrolled in the study. Participants were randomly administered loading doses of prasugrel 60 mg (group A, n = 166) or 30 mg (group B, n = 166) before undergoing elective PCI in a 1:1 manner. Primary efficacy end point was composite of in-hospital death and stent thrombosis at 96 h, while safety end point was in-hospital bleeding.

Results: The two groups did not differ in their baseline characteristics. The primary efficacy end point was 0.6% in both the conventional 60 mg loading dose (LD) and lower 30 mg LD groups (p = not significant). Minor bleeding was significantly less in group B [Bleeding Academic Research Consortium 1, A = 6.63% vs B = 1.81%, odds ratio (OR) = 3.86, 95% confidence interval (CI) = 1.06-14.08, P = 0.05]. Major bleeding was higher in group A (A = 3.61%, vs B = 1.81%, OR = 2.04, 95% CI = 0.50-8.29, P = 0.50).

Conclusion: In Indian patients, 30 mg of prasugrel loading is as effective as 60 mg of prasugrel with significantly less minor bleeding.
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http://dx.doi.org/10.1016/j.ihj.2018.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309884PMC
December 2018

Regioselective Synthesis of Chirally Enriched Tetrahydrocarbazolones and Tetrahydrocarbazoles.

Org Lett 2018 07 3;20(14):4240-4244. Epub 2018 Jul 3.

Department of Chemistry, School of Natural Sciences , Shiv Nadar University (SNU) , NH91, Tehsil-Dadri , Gautam Buddha Nagar , Uttar Pradesh 201314 , India.

A new one-step, reagent-directed regioselective synthesis of chirally enriched tetrahydrocarbazolones and tetrahydrocarbazoles from a common type of substrate has been developed. The salient features of this method include inherited stereodiversity, a broad substrate scope, a quick reaction time, and a benign catalyst. The method is applicable to the synthesis of a bioactive cryptosanguinolentine precursor.
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http://dx.doi.org/10.1021/acs.orglett.8b01656DOI Listing
July 2018

Correction: Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-c]quinolones as antiproliferative agents.

Org Biomol Chem 2018 03 5;16(12):2185. Epub 2018 Mar 5.

Department of Chemistry, School of Natural Sciences, Shiv Nadar University (SNU), NH91, Tehsil-Dadri, Gautam Buddha Nagar, Uttar Pradesh 201314, India.

Correction for 'Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-c]quinolones as antiproliferative agents' by Priti Kumari et al., Org. Biomol. Chem., 2018, DOI: 10.1039/c7ob03186f.
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http://dx.doi.org/10.1039/c8ob90031kDOI Listing
March 2018

Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-c]quinolones as antiproliferative agents.

Org Biomol Chem 2018 03 7;16(12):2049-2059. Epub 2018 Feb 7.

Department of Chemistry, School of Natural Sciences, Shiv Nadar University (SNU), NH91, Tehsil-Dadri, Gautam Buddha Nagar, Uttar Pradesh 201314, India. and Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.

Pyrano[3,2-c]quinolone structural motifs are commonly found in natural products with diverse biological activities. As part of a research programme aimed at developing the efficient synthesis of natural product-like small molecules, we designed and developed the microwave assisted, facile stereoselective synthesis of two series of carbohydrate fused pyrano[3,2-c]quinolone derivatives (n = 23) starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxyquinolones in shorter reaction times (15-20 min). The antiproliferative activity of these synthesized pyrano[3,2-c]quinolones was determined against MCF-7 (breast) and HepG2 (liver) cancer cells. The selected library members displayed low micromolar (3.53-9.68 μM) and selective antiproliferative activity. These findings on carbohydrate fused pyrano[3,2-c]quinolone derivatives are expected to provide new leads for anticancer drug discovery.
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http://dx.doi.org/10.1039/c7ob03186fDOI Listing
March 2018

Acute Fulminant Uremic Neuropathy Following Coronary Angiography Mimicking Guillain-Barre Syndrome.

Heart Views 2017 Apr-Jun;18(2):62-63

Department of Cardiology, JLN Hospital, Ajmer, Rajasthan, India.

A 55-year-old diabetic woman suffered a posterior wall ST-elevation myocardial infarction. She developed contrast-induced nephropathy following coronary angiography. Acute fulminant uremic neuropathy was precipitated which initially mimicked Guillan-Barre Syndrome, hence reported.
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http://dx.doi.org/10.4103/1995-705X.208673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501032PMC
July 2017

Ivabradine vs metoprolol in patients with acute inferior wall myocardial infarction-"Expanding arena for ivabradine".

Cardiovasc Ther 2017 Aug;35(4)

Escorts Heart Hospital, New Delhi, India.

Background: Atrioventricular (AV) blocks are of concern with the use of beta blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart rate with a lesser risk of AV blocks.

Objectives: To compare ivabradine with metoprolol in acute inferior wall MI in terms of feasibility, tolerability, and efficacy.

Methods: It was a prospective double-blind single-center randomized controlled study. Of 1032 patients with acute inferior wall MI, 468 eligible patients were randomized in 1:1 manner to ivabradine (group A) and metoprolol (group B). Intention to treat analysis of 426 patients (group A-232 and group B-232) was performed. The primary endpoint was 30-day incidence of major adverse cardiovascular events including death, reinfarction, complete heart block (CHB), and heart failure. Secondary endpoints included 30 days incidence of recurrent angina, readmission, first- or second-degree AV block, and tachyarrhythmias.

Results: Both the drugs decreased the mean heart rate to 62.22±2.95 (group A) vs 62.53±3.59 (group B) beats per minute (P=0.33). Ejection fraction improved in both the groups (5.15±1.93% in group A vs 5.52±2.18% in group B, P=0.065). The two groups did not differ significantly in their primary endpoints in terms of death (group A=1.72% vs group B=1.72%, OR=1.00, 95% CI=0.25-4.05, P=1.00), reinfarction (group A=0.86% vs group B=0.86%, OR=1.00, 95% CI=0.14-7.16, P=1.00), heart failure (group A=4.31% vs group B=2.59%, OR=1.70, 95% CI=0.61-4.75, P=0.31), or CHB (0% vs 2.59%, OR=0.07, 95% CI=0.00-1.34, P=0.08). There were no significant differences in the secondary endpoints of recurrent angina, readmission, and tachyarrhythmias except for more first- and second-degree AV blocks with metoprolol (12.93% vs 2.59%, OR=5.59, 95% CI=2.28-13.72, P=0.0002).

Conclusions: Ivabradine is well tolerated and equally effective as metoprolol in acute inferior wall ST elevation myocardial infarction patients for lowering the heart rate with lesser risk of AV blocks.
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http://dx.doi.org/10.1111/1755-5922.12266DOI Listing
August 2017

A phosphorylation-wide sncRNA screen reveals Protein Functional Effector sncRNAs (pfeRNAs) in human lung somatic cells.

Cancer Lett 2017 06 16;396:85-93. Epub 2017 Mar 16.

Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, University of Maryland, 650 W Baltimore St, Baltimore, MD, 21201, USA. Electronic address:

We recently reported that PIWI-interacting RNAs likes (piR-Ls) could regulate functions of the interacting phosphorylated proteins (p-Proteins). In addition, except for writers and erasers, functional efficacy of p-Proteins on their readers still remains unknown. We, therefore, reasoned there was a type of sncRNAs which could regulate functional efficacy of p-Proteins. Here, we profiled sncRNAs interacting with phosphorylated -Ser, -Thr and -Tyr residues in 3 HBE and 4 lung SCC cell lines, investigated effects and mechanisms of phosphorylated-residue-interacting sncRNAs. Our results demonstrated sncRNAs regulating functional efficacy of p-Proteins and we thus referred them as Protein Functional Effector sncRNAs (pfeRNAs). pfeRNAs were distributed among 26 to 50 nucleotides, shared some core sequences and showed distinctive expression patterns between HBE and SCC cells. Core sequences 417 (CS417), showing consistent upregulation in all 4 SCC cells, bound directly to p-Nucleolin (NCL), which was dependent on the key elements CGCG of CS417 and p-Ser619 of NCL. The CS417/p-NCL interaction was critical for functional efficacy of p-NCL in basic activities of lung normal and cancer cells. Thus, we revealed a novel type of pfeRNAs controlling functional efficacy of p-Proteins in lung somatic cells.
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http://dx.doi.org/10.1016/j.canlet.2017.03.017DOI Listing
June 2017

Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions.

Sci Rep 2016 10 18;6:35284. Epub 2016 Oct 18.

Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, 15 York St., New Haven, Connecticut, CT 06520 USA.

Babesia microti, a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite. Furthermore, we found that polymorphism is restricted to a small number of genes, which are highly expressed during infection. In order to identify pathogen-encoded factors involved in host-parasite interactions, we screened a proteome array comprised of 174 B. microti proteins, including several predicted members of the parasite secretome. Using this immuno-proteomic approach we identified several novel antigens that trigger strong host immune responses during the onset of infection. The genomic and immunological data presented herein provide the first insights into the determinants of B. microti interaction with its mammalian hosts and their relevance for understanding the selective pressures acting on parasite evolution.
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http://dx.doi.org/10.1038/srep35284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082761PMC
October 2016

An integrated genomic and transcriptomic survey of mucormycosis-causing fungi.

Nat Commun 2016 07 22;7:12218. Epub 2016 Jul 22.

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

Mucormycosis is a life-threatening infection caused by Mucorales fungi. Here we sequence 30 fungal genomes, and perform transcriptomics with three representative Rhizopus and Mucor strains and with human airway epithelial cells during fungal invasion, to reveal key host and fungal determinants contributing to pathogenesis. Analysis of the host transcriptional response to Mucorales reveals platelet-derived growth factor receptor B (PDGFRB) signaling as part of a core response to divergent pathogenic fungi; inhibition of PDGFRB reduces Mucorales-induced damage to host cells. The unique presence of CotH invasins in all invasive Mucorales, and the correlation between CotH gene copy number and clinical prevalence, are consistent with an important role for these proteins in mucormycosis pathogenesis. Our work provides insight into the evolution of this medically and economically important group of fungi, and identifies several molecular pathways that might be exploited as potential therapeutic targets.
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http://dx.doi.org/10.1038/ncomms12218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961843PMC
July 2016

3D Xplane Echocardiographic Technique for Validation of Mitral Leaflet Separation to Assess Severity of Mitral Stenosis.

Echocardiography 2016 Jun 29;33(6):896-901. Epub 2016 Jan 29.

ACE Heart and Vascular Institute, Mohali, Punjab, India.

Background: Determining the severity of mitral stenosis (MS) is important for both prognostic and therapeutic implications. Mitral valve area (MVA) calculation techniques have more limitations. Mitral leaflet separation (MLS) is a precise and operator friendly alternative to planimetry. In contrast to previous researchers, we have used a novel 3D Xplane technique to validate MLS for assessing the severity of MS. 3D Xplane is superior for validation of MLS due to simultaneous real time acquisition of MLS in parasternal long-axis view and corresponding MVA by planimetry in parsternal short-axis view.

Methods: It was a prospective observational single center study. A total of 174 patients with MS were evaluated for MVA estimation by various echocardiographic modalities. Maximum leaflet separation and corresponding planimetered MVA were measured using novel 3D Xplane technique.

Results: With 3D Xplane technique, there was strong positive correlation between planimetered MVA and MLS (R = 0.925, P < 0.001), irrespective of coexisting MR (R = 0.886, P < 0.001) or AF (R = 0.912, P < 0.001). Receiver operating characteristic curves of MLS demonstrated AUC for mild and severe MS to be 0.966 and 0.995, respectively. MLS less than 8.62 mm predicted severe MS with 95.5% sensitivity and 94.7% specificity and MLS more than 12.23 mm predicted mild MS with 93.2% sensitivity and 91.4% specificity.

Conclusion: In our study, a strong correlation between planimetered MVA and MLS was found using 3D Xplane technique. 3D Xplane thus validates and standardizes MLS by excluding errors due to temporal and spatial variations which are important limitations of 2D echocardiography.
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http://dx.doi.org/10.1111/echo.13183DOI Listing
June 2016

Sweating: A Specific Predictor of ST-Segment Elevation Myocardial Infarction Among the Symptoms of Acute Coronary Syndrome: Sweating In Myocardial Infarction (SWIMI) Study Group.

Clin Cardiol 2016 Feb 22;39(2):90-5. Epub 2015 Dec 22.

Department of Cardiology, Jawaharlal Nehru Medical College and Hospital, Ajmer, Rajasthan, India.

Background: Today, cardiologists seek to minimize time from symptom onset to interventional treatment for the most favorable results.

Hypothesis: In the acute coronary syndrome (ACS) symptom complex, sweating can differentiate ST-segment elevation myocardial infarction (STEMI) from non-ST-segment elevation ACS (NSTE-ACS) during early hours of infarction.

Methods: This single-center, prospective, observational study compared symptoms of STEMI and NSTE-ACS patients admitted from August 2012 to July 2014.

Results: Of 12 913 patients, 90.56% met ACS criteria. Among these, 22.51% had STEMI. Typical angina was the most common symptom (83.82%). On stepwise multiple regression, sweating (odds ratio: 97.06, 95% confidence interval [CI]: 82.16-114.14, P < 0.0001) and typical angina (odds ratio: 2.72, 95% CI: 2.18-3.38, P < 0.001) had significant association with STEMI. For diagnosis of STEMI, positive likelihood ratio (LR) and positive predictive value (PPV) were highest for typical angina with sweating (LR: 11.17, 95% CI: 10.31-12.1; PPV: 76.09, 95% CI: 74.37-77.75), followed by sweating with atypical angina (LR: 3.6, 95% CI: 3.07-4.21; PPV: 50.61, 95% CI: 46.45-54.76), typical angina (LR: 1.05, 95% CI: 1.03-1.07; PPV: 22.97, 95% CI: 22.11-23.84), and atypical angina (LR: 0.77, 95% CI: 0.69-0.87; PPV: 18.09, 95% CI: 16.32-19.97). C statistic values of 0.859 for typical angina with sweating and 0.519 for typical angina alone reflected high discriminatory value of sweating for STEMI prediction.

Conclusions: Presence of sweating with ACS symptoms predicts probability of STEMI, even before clinical confirmation. Sweating in association with typical or atypical angina is a much better predictor of STEMI than NSTE-ACS.
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http://dx.doi.org/10.1002/clc.22498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490850PMC
February 2016

Drosophila anti-nematode and antibacterial immune regulators revealed by RNA-Seq.

BMC Genomics 2015 Jul 11;16:519. Epub 2015 Jul 11.

Insect Infection and Immunity Lab, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, Washington DC, 20052, USA.

Background: Drosophila melanogaster activates a variety of immune responses against microbial infections. However, information on the Drosophila immune response to entomopathogenic nematode infections is currently limited. The nematode Heterorhabditis bacteriophora is an insect parasite that forms a mutualistic relationship with the gram-negative bacteria Photorhabdus luminescens. Following infection, the nematodes release the bacteria that quickly multiply within the insect and produce several toxins that eventually kill the host. Although we currently know that the insect immune system interacts with Photorhabdus, information on interaction with the nematode vector is scarce.

Results: Here we have used next generation RNA-sequencing to analyze the transcriptional profile of wild-type adult flies infected by axenic Heterorhabditis nematodes (lacking Photorhabdus bacteria), symbiotic Heterorhabditis nematodes (carrying Photorhabdus bacteria), and Photorhabdus bacteria alone. We have obtained approximately 54 million reads from the different infection treatments. Bioinformatic analysis shows that infection with Photorhabdus alters the transcription of a large number of Drosophila genes involved in translational repression as well in response to stress. However, Heterorhabditis infection alters the transcription of several genes that participate in lipidhomeostasis and metabolism, stress responses, DNA/protein synthesis and neuronal functions. We have also identified genes in the fly with potential roles in nematode recognition, anti-nematode activity and nociception.

Conclusions: These findings provide fundamental information on the molecular events that take place in Drosophila upon infection with the two pathogens, either separately or together. Such large-scale transcriptomic analyses set the stage for future functional studies aimed at identifying the exact role of key factors in the Drosophila immune response against nematode-bacteria complexes.
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http://dx.doi.org/10.1186/s12864-015-1690-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499211PMC
July 2015

A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells.

Nat Commun 2015 Jun 22;6:7316. Epub 2015 Jun 22.

1] Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, 650W Baltimore Street, Baltimore, Maryland 21201, USA [2] Marlene and Stewart Greenebaum Cancer Center, University of Maryland, 22S Greene Street, Baltimore, Maryland 21201, USA.

PIWI-interacting RNAs (piRNAs) are thought to silence transposon and gene expression during development. However, the roles of piRNAs in somatic tissues are largely unknown. Here we report the identification of 555 piRNAs in human lung bronchial epithelial (HBE) and non-small cell lung cancer (NSCLC) cell lines, including 295 that do not exist in databases termed as piRNA-like sncRNAs or piRNA-Ls. Distinctive piRNA/piRNA-L expression patterns are observed between HBE and NSCLC cells. piRNA-like-163 (piR-L-163), the top downregulated piRNA-L in NSCLC cells, binds directly to phosphorylated ERM proteins (p-ERM), which is dependent on the central part of UUNNUUUNNUU motif in piR-L-163 and the RRRKPDT element in ERM. The piR-L-163/p-ERM interaction is critical for p-ERM's binding capability to filamentous actin (F-actin) and ERM-binding phosphoprotein 50 (EBP50). Thus, piRNA/piRNA-L may play a regulatory role through direct interaction with proteins in physiological and pathophysiological conditions.
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http://dx.doi.org/10.1038/ncomms8316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557300PMC
June 2015

New signaling pathways govern the host response to C. albicans infection in various niches.

Genome Res 2015 May 9;25(5):679-89. Epub 2015 Apr 9.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;

Candida albicans, the major invasive fungal pathogen of humans, can cause both debilitating mucosal infections and fatal invasive infections. Understanding the complex nature of the host-pathogen interaction in each of these contexts is essential to developing desperately needed therapies to treat fungal infections. RNA-seq enables a systems-level understanding of infection by facilitating comprehensive analysis of transcriptomes from multiple species (e.g., host and pathogen) simultaneously. We used RNA-seq to characterize the transcriptomes of both C. albicans and human endothelial cells or oral epithelial cells during in vitro infection. Network analysis of the differentially expressed genes identified the activation of several signaling pathways that have not previously been associated with the host response to fungal pathogens. Using an siRNA knockdown approach, we demonstrate that two of these pathways-platelet-derived growth factor BB (PDGF BB) and neural precursor-cell-expressed developmentally down-regulated protein 9 (NEDD9)-govern the host-pathogen interaction by regulating the uptake of C. albicans by host cells. Using RNA-seq analysis of a mouse model of hematogenously disseminated candidiasis (HDC) and episodes of vulvovaginal candidiasis (VVC) in humans, we found evidence that many of the same signaling pathways are activated during mucosal (VVC) and/or disseminated (HDC) infections in vivo. Our analyses have uncovered several signaling pathways at the interface between C. albicans and host cells in various contexts of infection, and suggest that PDGF BB and NEDD9 play important roles in this interaction. In addition, these data provide a valuable community resource for better understanding host-fungal pathogen interactions.
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http://dx.doi.org/10.1101/gr.187427.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417116PMC
May 2015