Publications by authors named "Sangeeta Sharma"

87 Publications

Recent Advances in Diagnosis and Management of Female Genital Tuberculosis.

J Obstet Gynaecol India 2021 Aug 28:1-12. Epub 2021 Aug 28.

Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, Room No. 3064A, IIIrd Floor, Teaching Block, New Delhi, 110029 India.

Female genital tuberculosis (FGTB) is an important cause of significant morbidity and infertility. Gold-standard diagnosis by demonstration of acid fast bacilli on microscopy or culture or detection of epithelioid granuloma on histopathology of endometrial or peritoneal biopsy is positive in only small percentage of cases due to its paucibacillary nature. Use of gene Xpert on endometrial or peritoneal biopsy has improved sensitivity of diagnosis. Composite reference standard (CRS) is a significant landmark in its diagnosis in which combination of factors like AFB on microscopy or culture, positive gene Xpert, epithelioid granuloma on endometrial or peritoneal biopsy, demonstration of definite or probable findings of FGTB on laparoscopy or hysteroscopy. There have been many advances and changes in management of FGTB recently. The program is now called National Tuberculosis Elimination Program (NTEP), and categorization of TB has been stopped. Now, patients are divided into drug-sensitive FGTB for which rifampicin (R), isoniazid (H), pyrazinamide (Z) and ethambutol (E) are given orally daily for 2 months followed by three drugs (rifampicin, isoniazid and ethambutol (RHE) orally daily for next 4 months. Multi-drug-resistant FGTB is treated with shorter MDR TB regimen of 9-11 months or longer MDR TB regimen of 18-20 months with reserved drugs. In vitro fertilization and embryo transfer have good results for blocked tubes and receptive endometrium, while surrogacy or adoption is advised for severe grades of Asherman's syndrome.
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http://dx.doi.org/10.1007/s13224-021-01523-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402974PMC
August 2021

Spin/Valley Coupled Dynamics of Electrons and Holes at the MoS-MoSe Interface.

Nano Lett 2021 Sep 19;21(17):7123-7130. Epub 2021 Aug 19.

Department of Physics, Freie Universität Berlin, 14195 Berlin, Germany.

The coupled spin and valley degrees of freedom in transition metal dichalcogenides (TMDs) are considered a promising platform for information processing. Here, we use a TMD heterostructure MoS-MoSe to study optical pumping of spin/valley polarized carriers across the interface and to elucidate the mechanisms governing their subsequent relaxation. By applying time-resolved Kerr and reflectivity spectroscopies, we find that the photoexcited carriers conserve their spin for both tunneling directions across the interface. Following this, we measure dramatically different spin/valley depolarization rates for electrons and holes, ∼30 and <1 ns, respectively, and show that this difference relates to the disparity in the spin-orbit splitting in conduction and valence bands of TMDs. Our work provides insights into the spin/valley dynamics of photoexcited carriers unaffected by complex excitonic processes and establishes TMD heterostructures as generators of spin currents in spin/valleytronic devices.
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http://dx.doi.org/10.1021/acs.nanolett.1c01538DOI Listing
September 2021

Molecular docking analysis of pyruvate kinase M2 with a potential inhibitor from the ZINC database.

Bioinformation 2021 31;17(1):139-146. Epub 2021 Jan 31.

School of Life Sciences, IIMT University Meerut,India.

The pyruvate kinase M2 isoform (PKM2) is linked with cancer. Therefore, it is of interest to document the molecular docking analysis of Pyruvate Kinase M2 (PDB ID: 4G1N) with potential activators from the ZINC database. Thus, we document the optimal molecular docking features of a compound having ID ZINC000034285235 with PKM2 for further consideration.
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http://dx.doi.org/10.6026/97320630017139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340708PMC
January 2021

Dynamics of carbon storage and status of standing vegetation in temperate coniferous forest ecosystem of north western Himalaya India.

Vegetos 2021 Jul 28:1-12. Epub 2021 Jul 28.

School of Studies in Botany, Jiwaji University, Gwalior, India.

Natural ecosystems, which operate as a sink, play an important role in determining the concentration of CO in the atmosphere and have a large storage capacity, assisting in mitigation of problem that has a negative impact on the human population. Forests are one of the most important carbon sinks in the terrestrial ecosystem, with the best example being the Western Himalaya, where healthy and sustainable vegetation is prized. Standard methodology was adopted for assessing the different parameters of carbon related information to enumerate the status of carbon storage and its trend in sustaining the ecosystem of the area. The current research displays the annual increment and carbon dynamics in various vegetation components and levels. Trees, shrubs, and herbs help to fix atmospheric carbon in a variety of forms, including AGC, BGC, and TC. The concentration of carbon-fixing potential was measured on an annual and seasonal basis, with herbs having the highest mean annual increment, followed by shrubs and trees.  had the largest annual carbon stock change among trees, followed by , , and . topped the increase percentage with 60.58%, followed by 33.35%, 5.61%, and 0.45%. Litter was also investigated as a potential source of mitigation, with the best results observed during the autumn months. Natural coniferous forests provide a regulating ecological service in the region by maintaining carbon dioxide levels in the form of biomass, according to the study.
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http://dx.doi.org/10.1007/s42535-021-00265-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316892PMC
July 2021

The Ethnic Identity Scale: Affirmation, really?

Cultur Divers Ethnic Minor Psychol 2021 Jul 22. Epub 2021 Jul 22.

Department of Psychology.

Objective: The Ethnic Identity Scale (EIS) was developed to distinguish between process and content components of ethnic-racial identity (ERI). However, the affirmation subscale is composed entirely of negatively worded items, measuring negative feelings about one's ethnic-racial group, rather than positive feelings as widely conceptualized. Addressing this gap, the present study examined the psychometric validity of a revised EIS with positively and negatively worded items to determine whether affirmation is best represented as a unidimensional construct, a bidimensional construct, or a combination of the two.

Method: The sample consisted of 280 college students (75.5% female; = 20.95 years; = 1.98 years). The largest ethnic-racial group consisted of Black or African Americans (68.2%), followed by Asian/Asian Americans (12.1%), Hispanic/Latinos (9.6%), and other ethnic-racial groups (10%).

Results: Confirmatory factor analysis provided evidence for both unidimensionality and multidimensionality. Indeed, although positively worded and negatively worded items of "affirmation" loaded onto a general factor representing affirmation, there was still a significant amount of variance captured by the negative ERI affect specific factor, indicating the presence of multidimensionality. In addition, results indicated that negative ERI affect, over and above the general ERI affirmation factor, predicted psychosocial functioning.

Conclusions: The present study expands our understanding of the multidimensionality of ERI, highlighting the need for examination of how we measure ERI affect at the very least, and possibly how we conceptualize it within the broader ERI literature. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/cdp0000485DOI Listing
July 2021

Antiseizure Drug Levels in Children Aged 2-12 Years Presenting With Breakthrough Seizures: A Single Center Cross-sectional Study.

Indian Pediatr 2021 Sep 28;58(9):850-852. Epub 2021 Jun 28.

Department of Statistics, Delhi Cancer Registry, Dr. BRAIRCH, AIIMS, New Delhi.

Objectives: To study the antiseizure drug levels and associated factors in children with breakthrough seizures.

Methods: This cross-sectional study conducted at a public hospital from November, 2017 to April, 2019, included 145 children with epilepsy aged 2 to 12 years presenting with breakthrough seizure. Antiseizure drug levels were measured, and the levels were categorized as within, below, and above the reference range.

Results: Children with epilepsy receiving sodium valproate, phenytoin and carbamazepine were 111 (73%), 31 (20.4%) and 10 (6.6%), respectively, of which 7 were receiving multiple antiseizure drugs. Drug levels below the reference range were found in 64 (44.1%), within the reference range in 70 (48.3%), and the above reference range in 11 (7.6%) children.

Conclusions: Nearly half the children with breakthrough seizures had sub-therapeutic levels, especially those on phenytoin therapy. Drug levels in below therapeutic range were not associated with occurrence of breakthrough seizures.
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September 2021

Conversion of five proluciferin esters by human cytochrome P450 enzymes.

Biotechnol J 2021 Jul 25;16(7):e2100007. Epub 2021 May 25.

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, China.

Background: Probe substrates are an important tool for activity monitoring of human drug metabolizing enzymes such as cytochromes P450 (CYPs).

Brief Methods: In the present study we have tested human CYPs for metabolization of five proluciferin ester substrates which had previously only been known to be hydroxylated by CYP26A1.

Major Results: It was found that these substrates were converted by another 21 human CYPs, which belong to the CYP families 1 to 4, 7, and 26. Thus, 66 new pairs of enzyme and substrate were identified. Correlation analysis indicated the presence of three distinct sets of enzymes with high similarity in their activity profiles that encompass a total of 16 individual enzymes.

Conclusions: Some of these newly identified correlations may serve as a starting point for further study of those human CYPs whose activities are not yet satisfactorily understood.
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http://dx.doi.org/10.1002/biot.202100007DOI Listing
July 2021

Tuberculosis (TB) in pregnancy - A review.

Eur J Obstet Gynecol Reprod Biol 2021 Apr 19;259:167-177. Epub 2021 Feb 19.

Department of Obstetrics and Gynaecology, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Nigeria.

Tuberculosis (TB) is a common infectious pathology especially in low-income countries, which may complicate pregnancy. Although pulmonary TB is more common in pregnancy than extra pulmonary TB (EPTB), EPTB is becoming more common especially in those living with human deficiency virus (HIV) co infection or have other comorbidities. The diagnosis of TB may be delayed in pregnancy due to the masking of its symptoms by those of pregnancy. If diagnosed and treated on time both pulmonary TB and EPTB are associated with excellent maternal and perinatal outcome. If, however, there is delay in diagnosis and treatment then there could be adverse maternal and fetal consequences like preterm labour, fetal growth restriction and even stillbirths. Similarly severe forms of TB like disseminated disease (miliary TB) or multi drug resistant TB (MDR TB) are associated with poor outcome. Diagnosis and management is same as in non-pregnant patients. Both drug sensitive pulmonary TB and EPTB are treated with four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) orally daily for 2 months followed by three drugs (isoniazid, rifampicin and ethambutol) orally daily for 4 months. Drug resistant TB is treated with second line drugs with caution, as some of these drugs are teratogenic. Optimum antenatal care and nutrition therapy along with anti-tuberculosis drugs provide for optimum maternal and perinatal outcome. This review discusses maternal and perinatal outcomes, diagnosis and management of pulmonary TB and extrapulmonary TB as well as perinatal tuberculosis.
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http://dx.doi.org/10.1016/j.ejogrb.2021.02.016DOI Listing
April 2021

Highlights of pre conference workshop on paediatric tuberculosis.

Authors:
Sangeeta Sharma

Indian J Tuberc 2021 01 13;68(1):139-141. Epub 2021 Jan 13.

Department of Paediatrics, National Institute of TB and Respiratory Diseases, New Delhi 110029, India. Electronic address:

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http://dx.doi.org/10.1016/j.ijtb.2021.01.001DOI Listing
January 2021

Study of Helicity-Dependent Light-Induced Demagnetization: From the Optical Regime to the Extreme Ultraviolet Regime.

Nano Lett 2021 Mar 19;21(5):1943-1947. Epub 2021 Feb 19.

Université de Lorraine, LPCT, CNRS, UMR 7019, BP 70239, 54506 Cedex Vandoeuvre-lès-Nancy, France.

We use real-time time-dependent density functional theory to investigate the effect of optical and extreme ultraviolet (XUV) circularly polarized femtosecond pulses on the magnetization dynamics of ferromagnetic materials. We demonstrate that the light induces a helicity-dependent reduction of the magnitude of the magnetization. In the XUV regime, where the 3p semicore states are involved, a larger helicity dependence persisting even after the passage of light is exhibited. Finally, we were able to separate the part of the helicity-dependent dynamics due to the absorption from the part due to the inverse Faraday effect. Doing so, we show that the former has, overall, a greater impact on the magnetization than the latter, especially after the pulse and in the XUV regime. This work hints at the yet experimentally unexplored territory of the XUV light-induced helicity-dependent dynamics, which, according to our prediction, could magnify the helicity-dependent dynamics already exhibited in the optical regime.
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http://dx.doi.org/10.1021/acs.nanolett.0c04166DOI Listing
March 2021

Genital tb-diagnostic algorithm and treatment.

Indian J Tuberc 2020 Dec 15;67(4S):S111-S118. Epub 2020 Oct 15.

Medical Officer, Department of Obstetrics & Gynecology, Atal Bihari Vajpayee Institute of Medical Sciences, New Delhi, India.

Female genital tuberculosis (FGTB) is a common cause of infertility in India but its diagnosis remains elusive due to paucibacillary nature of disease. Traditional methods of diagnosis include demonstration of acid fast bacilli on endometrial or peritoneal biopsy or epithelioid granuloma on the biopsy or positive gene Xpert on the biopsy, but they are positive in small percentage of cases only missing diagnosis in many cases. Positive polymerase chain reaction (PCR) alone is not taken for diagnosis due to high false positivity. Diagnostic laparoscopy and hysteroscopy can detect many cases by direct demonstration of TB lesions. Composite reference standard is a useful method to diagnose FGTB. This review discusses various diagnostic modalities including endometrial or peritoneal biopsy to detect acid fast bacilli on microscopic or culture or epithelioid granuloma, role of PCR, role of radiological imaging (hysterosalpingography, ultrasound, CT scan, MRI and PET-CT scan) and role of endoscopic techniques (laparoscopy and hysteroscopy) in diagnosis of FGTB including role of composite reference standard. The International and National studies highlight the role of composite reference standard and its components like demonstration of AFB on microscopy or culture of endometrial or peritoneal biopsy or epithelioid granuloma or gene Xpert or PCR or latest tests like loop-mediated isothermal amplification (TB-LAMP) test and other newer molecular methods like Xpert Ultra for diagnosis of FGTB. It also detects role of endoscopy in FGTB and role of diagnostic algorithm for diagnosis of FGTB. Treatment is with four primary drugs (rifampicin, isoniazid, ethambutol and pyrazinamide) for two months followed by three drugs (rifampicin, isoniazid and ethambutol) daily orally for 4 months for drug sensitive FGTB. Shorter Multidrug-resistant TB (MDR-TB) regimen is given for Rifampicin resistant (RR)/MDR confined to only FGTB while longer all oral regimen is given for RR/MDR with or without additional drug resistance, HIV seropositives with FGTB or involvement of other sites or pulmonary TB (PTB) along with FGTB. Composite reference standard which combines various diagnostic modalities is a useful strategy to diagnose FGTB.
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http://dx.doi.org/10.1016/j.ijtb.2020.10.005DOI Listing
December 2020

New luciferin-based probe substrates for human CYP26A1.

Biochem Biophys Rep 2020 Dec 23;24:100861. Epub 2020 Nov 23.

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, 300072, China.

Activity of human CYP26A1 towards six proluciferin probe substrates and their ester derivatives was monitored. These included three monofluorobenzyl ether isomers and three five-membered heterocycles. Overall, luciferin substrates with a free acid group gave higher activities than the ester compounds. Also, luciferin derivatives with six-ring structures were better metabolized than those with five-rings. The best substrates identified in this study are Luciferin 6' 3-fluorobenzyl ether (Luciferin-3FBE) and its methyl ester (Luciferin-3FBEME). Taken together, we describe eleven new probe substrates for CYP26A1 and demonstrate for the first time that CYP26A1 does not only accept acid substrates but can also metabolize esters.
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http://dx.doi.org/10.1016/j.bbrep.2020.100861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695906PMC
December 2020

Recommendations for prenatal, intrapartum, and postpartum care during COVID-19 pandemic in India.

Am J Reprod Immunol 2020 11 21;84(5):e13336. Epub 2020 Sep 21.

Department of Obstetrics & Gynecology, All India Institute of Medical Sciences, New Delhi, India.

The pandemic of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 19.7 million persons worldwide with 7 28 013 deaths till August 10, 2020. It has put an unprecedented workload on healthcare systems with special reference to labor rooms and obstetrics as deliveries cannot be stopped or postponed. Preparing their facilities using triage (COVID-positive patients, COVID-suspect patients, and COVID-negative patients) can help to better utilize the limited resources and help in prevention of spread of disease, and improve maternal and perinatal outcome. There is a need for proper training of healthcare providers for judicious use of personal protective equipment (PPE) for optimum outcome. Fortunately, the available literature suggests that there is no substantial increased risk of acquiring COVID-19 in pregnancy or its increased virulence in pregnancy and labor and there are no adverse effects on fetus and neonate with negligible fetal transmission rate. Nevertheless, utmost care is needed to manage such pregnancies, their prenatal care, and labor. This review aimed to highlight the main recommendations applied in Indian maternities for better management of pregnancy during the COVID-19 pandemic.
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http://dx.doi.org/10.1111/aji.13336DOI Listing
November 2020

Demographic profile, clinical and microbiological predictors of mortality amongst admitted pediatric TB patients in a tertiary referral tuberculosis hospital.

Indian J Tuberc 2020 Jul 21;67(3):312-319. Epub 2019 Oct 21.

Department of Paediatrics, National Institute of TB & Respiratory Diseases, New Delhi 110030, India.

Background: Pediatric tuberculosis (TB) constitutes 8% of the total caseload of TB. Children are particularly vulnerable to dissemination of disease and mortality.

Aim: To determine mortality rate, elucidate type of TB, causes and predictors of mortality, if any, in admitted pediatric TB patients.

Methods: Present retrospective study was conducted in a tertiary referral center over last 6½ year on children who died out of total TB admissions.

Results: Out of total 1380 pediatric (<15 years of age) TB admissions, 74 children died, a mortality rate of 5.36%. Mean age was 11.4 years with highest mortality 47 (63.51%) in patients from 11 to 14 years age group. Significant majority 58 (78.38%) patients were females (p < 0.011). Range of hospital stay was 0-113 days with 7 (9.5%), 9 (12.16%) and 27 (36.48%) children dying on day of admission, next day and 3rd-7th day respectively, therefore a total of 43 (58.11%) died within first week of admission. Most 60 (81.08%) patients belonged to poor socio-economic status. History of contact was present in 12 (16.22%) cases while none had diabetes. 31 (41.89%) patients had sepsis and severe anemia (Hb ≤ 6 g %) was present in 6 (8.11%) patients at admission, out of which 4 died on the same day of admission, even before blood could be arranged. Most patients 68 (91.89%) had pulmonary TB with 25 children having concomitant extrapulmonary involvement, while 4 (5.41%) had meningeal TB and 2 (2.70%) had disseminated TB with HIV. Microbiological confirmation was achieved in 51 (68.92%) (48 PTB and 3 EPTB) cases while 23 (31.08%) were clinically diagnosed. Bilateral extensive fibro-cavitary disease with infiltrations was the commonest. Drug resistance was confirmed in 21 (28.38%) with 2, 5, 8, 5 and 1 patient diagnosed with mono H, RR, MDR, pre-XDR and XDR respectively but results of 9 patients were received posthumously. Treatment given was category 1, category 2 and regimens for drug resistant TB in 24 (32.43%), 29 (39.19%) and 21 (28.37%) cases respectively based on prior history of ATT and drug sensitivity. Adverse drug reactions were noted in 12 (16.21%) cases. Noted immediate causes of mortality were cardio-respiratory failure, sudden pneumothorax, massive hemoptysis, sepsis, extensive pulmonary disease and aspiration pneumonia. The pointers towards mortality include female gender, severe malnutrition, anemia, extensive disseminated disease and drug resistant TB. Ignorance, dependency of children on parents, poor adherence and late referrals into the system lead to delayed diagnosis and initiation of proper regimen based treatment.

Conclusion: Early referrals of non-responders and failures to centers equipped with programmatic management facilities are essential for proper, timely management of pediatric TB to reduce mortality.
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http://dx.doi.org/10.1016/j.ijtb.2019.10.001DOI Listing
July 2020

Screening of the whole human cytochrome P450 complement (CYPome) with enzyme bag cocktails.

J Pharm Anal 2020 Jun 26;10(3):271-276. Epub 2020 May 26.

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, 300072, China.

We have previously introduced the use of permeabilized fission yeast cells (enzyme bags) that recombinantly express full-length CYPs for drug metabolism studies. Such enzyme bags are cells with pores that function as enzymes . They can easily be prepared without a need for ultracentrifugation and may be used in similar protocols as microsomes. In this study we report the preparation of enzyme bag cocktails that permit the testing of multiple CYPs in a single enzyme bag reaction. Moreover, we established a convenient testing scheme that permits a rapid screen of all human CYPs for activity towards any given candidate substrate. An important aspect of this approach is the reduction of individual CYP test assays. If a cocktail containing many CYPs tests negative, it follows that all CYPs included in that cocktail need not be tested individually, thus saving time and resources. The new protocol was validated using two probe substrates.
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http://dx.doi.org/10.1016/j.jpha.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322738PMC
June 2020

Downregulation of peripheral PTGS2/COX-2 in response to valproate treatment in patients with epilepsy.

Sci Rep 2020 02 13;10(1):2546. Epub 2020 Feb 13.

Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi, 110007, India.

Antiepileptic drug therapy has significant inter-patient variability in response towards it. The current study aims to understand this variability at the molecular level using microarray-based analysis of peripheral blood gene expression profiles of patients receiving valproate (VA) monotherapy. Only 10 unique genes were found to be differentially expressed in VA responders (n = 15) and 6 genes in the non-responders (n = 8) (fold-change >2, p < 0.05). PTGS2 which encodes cyclooxygenase-2, COX-2, showed downregulation in the responders compared to the non-responders. PTGS2/COX-2 mRNA profiles in the two groups corresponded to their plasma profiles of the COX-2 product, prostaglandin E (PGE). Since COX-2 is believed to regulate P-glycoprotein (P-gp), a multidrug efflux transporter over-expressed at the blood-brain barrier (BBB) in drug-resistant epilepsy, the pathway connecting COX-2 and P-gp was further explored in vitro. Investigation of the effect of VA upon the brain endothelial cells (hCMEC/D3) in hyperexcitatory conditions confirmed suppression of COX-2-dependent P-gp upregulation by VA. Our findings suggest that COX-2 downregulation by VA may suppress seizure-mediated P-gp upregulation at the BBB leading to enhanced drug delivery to the brain in the responders. Our work provides insight into the association of peripheral PTGS2/COX-2 expression with VA efficacy and the role of COX-2 as a potential therapeutic target for developing efficacious antiepileptic treatment.
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http://dx.doi.org/10.1038/s41598-020-59259-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018850PMC
February 2020

Optical inter-site spin transfer probed by energy and spin-resolved transient absorption spectroscopy.

Nat Commun 2020 Feb 13;11(1):871. Epub 2020 Feb 13.

Max Born Institute for Nonlinear Optics and Short Pulse Spectroscopy, Max-Born-Strasse 2A, 12489, Berlin, Germany.

Optically driven spin transport is the fastest and most efficient process to manipulate macroscopic magnetization as it does not rely on secondary mechanisms to dissipate angular momentum. In the present work, we show that such an optical inter-site spin transfer (OISTR) from Pt to Co emerges as a dominant mechanism governing the ultrafast magnetization dynamics of a CoPt alloy. To demonstrate this, we perform a joint theoretical and experimental investigation to determine the transient changes of the helicity dependent absorption in the extreme ultraviolet spectral range. We show that the helicity dependent absorption is directly related to changes of the transient spin-split density of states, allowing us to link the origin of OISTR to the available minority states above the Fermi level. This makes OISTR a general phenomenon in optical manipulation of multi-component magnetic systems.
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http://dx.doi.org/10.1038/s41467-020-14691-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018696PMC
February 2020

Altered plasma prostaglandin E levels in epilepsy and in response to antiepileptic drug monotherapy.

Prostaglandins Leukot Essent Fatty Acids 2020 02 22;153:102056. Epub 2020 Jan 22.

Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), Council of Scientific and Industrial Research (CSIR), Delhi 110007, India. Electronic address:

Prostaglandin E (PGE), a physiologically active lipid compound, is increased in several diseases characterized by chronic inflammation. To determine its significance in epilepsy-associated inflammation and response to antiepileptic drug (AED), we evaluated the plasma PGE (median, pg/ml) levels in drug-free patients with epilepsy (N = 34) and patients receiving AED monotherapy (N = 55) in addition to that in healthy controls (N = 34). When compared to controls, plasma PGE levels were significantly elevated in all drug-free patients independent of the type of epilepsy (137.2 versus 475.7 pg/ml, p < 0.0001). Among the patients receiving AED monotherapy, only valproate responders showed a significant decrease compared to both drug-free patients (232.1 versus 475.7 pg/ml, p < 0.01) as well as valproate non-responders (232.1 versus 611.9 pg/ml, p < 0.0001). Both responders and non-responders on phenytoin or carbamazepine monotherapy had elevated PGE levels similar to drug-free patients. In addition, no difference was observed in plasma profiles of PGE precursor, arachidonic acid among the groups. Our work presents the clinical evidence of the association between plasma PGE levels and valproate efficacy in patients with epilepsy.
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http://dx.doi.org/10.1016/j.plefa.2020.102056DOI Listing
February 2020

Perfect and Controllable Nesting in Minimally Twisted Bilayer Graphene.

Nano Lett 2020 Feb 13;20(2):971-978. Epub 2020 Jan 13.

Lehrstuhl für Theoretische Festkörperphysik , Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) , Staudtstraße 7-B2 , 91058 Erlangen , Germany.

Parallel ("nested") regions of a Fermi surface (FS) drive instabilities of the electron fluid, for example, the spin density wave in elemental chromium. In one-dimensional materials, the FS is trivially fully nested (a single nesting vector connects two "Fermi dots"), while in higher dimensions only a fraction of the FS consists of parallel sheets. We demonstrate that the tiny angle regime of twist bilayer graphene (TBLG) possesses a phase, accessible by interlayer bias, in which the FS consists entirely of nestable "Fermi lines", the first example of a completely nested FS in a two-dimensional (2D) material. This nested phase is found both in the ideal as well as relaxed structure of the twist bilayer. We demonstrate excellent agreement with recent STM images of topological states in this material and elucidate the connection between these and the underlying Fermiology. We show that the geometry of the Fermi lines network is controllable by the strength of the applied interlayer bias, and thus TBLG offers unprecedented access to the physics of FS nesting in 2D materials.
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http://dx.doi.org/10.1021/acs.nanolett.9b04027DOI Listing
February 2020

Emerging trends in microbiological diagnostics in children.

Indian J Tuberc 2019 Oct;66(4):549-554

Department of Microbiology, India.

The targets of the WHO's End TB Strategy and the United Nations' (UN) Sustainable Development Goals (SDGs) have been expanded to"Find. Treat. All #EndTB" with universal access to TB diagnosis, treatment and care by 2022 in an effort to end the global TB epidemic. Trends to achieve the above targets in children have led to greater emphasis on the newer diagnostics paving way to microbiological confirmation and universal drug sensitivity in children.
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http://dx.doi.org/10.1016/j.ijtb.2019.11.007DOI Listing
October 2019

Identification of new probe substrates for human CYP20A1.

Biol Chem 2020 02;401(3):361-365

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin 300072, China.

CYP20A1 is a well-conserved member of the human cytochrome P450 enzyme family for which no endogenous or xenobiotic substrate is known. We have recently shown that this enzyme has moderate activity towards two proluciferin probe substrates. In order to facilitate the search for physiological substrates we have tested nine additional proluciferins in this study and identified three such probe substrates that give much higher product yields. Using one of these probes, we demonstrate inhibition of CYP20A1 activity by 1-benzylimidazole, ketoconazole and letrozole. Finally, we show that the combination of two common single nucleotide polymorphisms (SNPs) of CYP20A1 leads to an enzyme (CYP20A1Leu97Phe346) with reduced activity.
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http://dx.doi.org/10.1515/hsz-2019-0307DOI Listing
February 2020

Light-wave dynamic control of magnetism.

Nature 2019 07 26;571(7764):240-244. Epub 2019 Jun 26.

Max-Planck-Institute of Quantum Optics, Garching, Germany.

The enigmatic interplay between electronic and magnetic phenomena observed in many early experiments and outlined in Maxwell's equations propelled the development of modern electromagnetism. Today, the fully controlled evolution of the electric field of ultrashort laser pulses enables the direct and ultrafast tuning of the electronic properties of matter, which is the cornerstone of light-wave electronics. By contrast, owing to the lack of first-order interaction between light and spin, the magnetic properties of matter can only be affected indirectly and on much longer timescales, through a sequence of optical excitations and subsequent rearrangement of the spin structure. Here we introduce the regime of ultrafast coherent magnetism and show how the magnetic properties of a ferromagnetic layer stack can be manipulated directly by the electric-field oscillations of light, reducing the magnetic response time to an external stimulus by two orders of magnitude. To track the unfolding dynamics in real time, we develop an attosecond time-resolved magnetic circular dichroism detection scheme, revealing optically induced spin and orbital momentum transfer in synchrony with light-field-driven coherent charge relocation. In tandem with ab initio quantum dynamical modelling, we show how this mechanism enables the simultaneous control of electronic and magnetic properties that are essential for spintronic functionality. Our study unveils light-field coherent control of spin dynamics and macroscopic magnetic moments in the initial non-dissipative temporal regime and establishes optical frequencies as the speed limit of future coherent spintronic applications, spin transistors and data storage media.
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http://dx.doi.org/10.1038/s41586-019-1333-xDOI Listing
July 2019

Nitric oxide induced modulations in adventitious root growth, lignin content and lignin synthesizing enzymes in the hypocotyls of Vigna radiata.

Plant Physiol Biochem 2019 Aug 29;141:225-230. Epub 2019 May 29.

Department of Botany, Panjab University, Chandigarh, 160014, India; Central University of Punjab, Mansa Road, Bathinda, 151001, India.

The present study evaluated the role of nitric oxide (NO) in mediating adventitious root (AR) growth, lignification and related enzymatic changes in the hypocotyls of Vigna radiata. To meet the objectives, the changes in AR growth, lignin content, and the activities of enzymes-peroxidases, polyphenol oxidases, and phenylalanine ammonia lyases- with NO donor and its scavenger were monitored. Hypocotyls were cultivated in aqueous solution supplemented with different concentrations of SNP (sodium nitroprusside, NO donor compound) and its scavenging compound (2,4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; cPTIO). Specifically, at low concentrations, SNP induced AR growth, increased the total lignin content and altered the activities of related oxidoreductases- peroxidases, polyphenol oxidases and phenylalanine ammonia lyases- which are involved in lignin biosynthesis pathway. At higher concentrations, a decline in AR growth and lignification was noticed. We analysed the function of NO in AR formation by depleting the endogenous NO using scavenging compound cPTIO. Hypocotyls grown in a medium supplemented with scavenger cPTIO exhibited significant decline in AR growth and the activities of lignin synthesizing enzymes. Application of NO scavenger showed that stimulatory properties on root lignification may be owing to NO itself. In addition, changes in AR growth were significantly correlated with these modified biochemical activities. Our analysis revealed that NO supplementation induces prominent alterations in lignin level during AR formation and this might be due to an alteration in the activity of lignin biosynthetic enzymes, which further affected the polymerization of monolignols and AR growth.
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http://dx.doi.org/10.1016/j.plaphy.2019.05.028DOI Listing
August 2019

Female genital tuberculosis: Revisited.

Indian J Med Res 2018 12;148(Suppl):S71-S83

Department of Obstetrics & Gynaecology, All India Institute of Medical Sciences, New Delhi, India.

Female genital tuberculosis (FGTB) is caused by Mycobacterium tuberculosis (rarely Mycobacterium bovis and/or atypical mycobacteria) being usually secondary to TB of the lungs or other organs with infection reaching through haematogenous, lymphatic route or direct spread from abdominal TB. In FGTB, fallopian tubes are affected in 90 per cent women, whereas uterine endometrium is affected in 70 per cent and ovaries in about 25 per cent women. It causes menstrual dysfunction and infertility through the damage of genital organs. Some cases may be asymptomatic. Diagnosis is often made from proper history taking, meticulous clinical examination and judicious use of investigations, especially endometrial aspirate (or biopsy) and endoscopy. Treatment is through multi-drug antitubercular treatment for adequate time period (rifampicin, isoniazid, pyrazinamide, ethambutol daily for 60 days followed by rifampicin, isoniazid, ethambutol daily for 120 days). Treatment is given for 18-24 months using the second-line drugs for drug-resistant (DR) cases. With the advent of increased access to rapid diagnostics and newer drugs, the management protocol is moving towards achieving universal drug sensitivity testing and treatment with injection-free regimens containing newer drugs, especially for new and previously treated DR cases.
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http://dx.doi.org/10.4103/ijmr.IJMR_648_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469382PMC
December 2018

Emerging treatment trends in pediatric TB.

Authors:
Sangeeta Sharma

Indian J Tuberc 2019 Jan 27;66(1):214-217. Epub 2019 Feb 27.

National Institute of TB & Respiratory Diseases, Sri Aurobindo Marg, New Delhi, 110030, India. Electronic address:

The WHO's End TB Strategy and the United Nations' (UN) Sustainable Development Goals (SDGs) share the common aim to end the global TB epidemic. Specific targets have been set in the End TB Strategy, for the period 2016-2035, which include a 90% reduction in TB deaths and an 80% reduction in TB incidence (new cases per year) by 2030, in comparison with 2015. Globally, though the TB incidence and mortality is falling at the rate of about 2% and 3% per year, by 2020, these figures need to improve to 4-5% per year and 10%, respectively, so that incidence can fall faster to reach the first (2020) milestones of the End TB Strategy. Newer treatment trends have emerged to achieve these targets in children.
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http://dx.doi.org/10.1016/j.ijtb.2019.02.010DOI Listing
January 2019

Diagnostic accuracy of loop-mediated isothermal amplification assay for extra-pulmonary tuberculosis in Indian population.

J Microbiol Methods 2019 03 28;158:59-65. Epub 2019 Jan 28.

Department of Paediatrics, National Institute of Tuberculosis and Respiratory Diseases, Sri Aurobindo Marg, New Delhi, India.

Background: Confirmatory diagnosis of extra-pulmonary tuberculosis remains a true challenge owing to difficulty in procuring appropriate specimen, inefficient laboratory methods and paucibacillary nature of infection. These obstructions become all the very difficult in pediatric EPTB cases, due to non-specific clinical signs and symptoms, low sensitivity of smear microscopy and culture, lack of awareness among clinicians, etc. AIM OF THE STUDY: The present study aimed to evaluate the diagnostic accuracy of rapid and cost-effective loop-mediated isothermal amplification (LAMP) assay for EPTB diagnosis in children.

Methods: A total of 154 cases were analyzed by EPTB-site smear microscopy, culture, PCRs for IS6110, MPB64 & Pab genes, nested PCR and LAMP assay. Single-gene PCRs were performed by custom-synthesized primers. Nested PCR was performed using the 3B BIOTUB Kit and the LAMP assay was done using the Nu-LAMP TB kit.

Results: We observed that the molecular tests displayed 4-fold higher positivity rate (minimum 46%) in comparison to the microbiological tests (maximum 11.03%). In contrast to the composite reference standard, LAMP assay was found to be 79.6% sensitive and 78% specific for EPTB diagnosis in childhood cases.

Conclusions: Our results indicate that LAMP assay is a promising technique for efficient diagnosis of EPTB in children belonging to resource-limited regions.
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http://dx.doi.org/10.1016/j.mimet.2019.01.016DOI Listing
March 2019

IV Levetiracetam versus IV Phenytoin in Childhood Seizures: A Randomized Controlled Trial.

J Pediatr Neurosci 2018 Apr-Jun;13(2):158-164

Department of Neuropsychopharmacology, Institute of Human Behaviour and Allied Sciences Delhi - 110095 India.

Objectives: To compare the efficacy of IV phenytoin and IV levetiracetam in acute seizures.

Design: Randomized controlled trial.

Setting: Tertiary care hospital, November 2012 to April 2014.

Patients: 100 children aged 3-12 yrs of age presenting with acute seizures.

Intervention: Participants randomly received either IV phenytoin 20 mg/kg ( = 50) or IV levetiracetam 30 mg/kg ( = 50). Patients who were had seizures at presentation received IV diazepam prior to these drugs.

Outcome Measures: Absence of seizure activity within next 24 hrs. Stopping of clinical seizure activity within 20 mins of first intervention, change in cardiorespiratory parameters, and achievement of therapeutic drug levels.

Results: Two groups were comparable in patient characteristics and seizure type ( > 0.05). Of the 100 children, 3 in levetiracetam and 2 in phenytoin group had a repeat seizure in 24 hrs, efficacy was comparable (94% vs 96%, > 0.05). Of these, 18 (36%) in phenytoin and 12 (24%) in levetiracetam group received diazepam. Sedation time was 178.80 ±97.534 mins in phenytoin and 145.50 ±105.208 mins in levetiracetam group ( = 0.346). Changes in cardiorespiratory parameters were similar in both groups except a lower diastolic blood pressure with phenytoin ( = 0.023). Therapeutic drug levels were achieved in 38 (76%) children both at 4 and 24 hrs with phenytoin, compared to 50 (100%) and 48 (98%) at 1 and 24 hrs with levetiracetam ( < 0.05).

Conclusion: Intravenous levetiracetam and phenytoin have similar efficacy in preventing seizure recurrences for 24 hrs in children 3-12 years presenting with acute seizures.
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http://dx.doi.org/10.4103/jpn.JPN_126_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057176PMC
August 2018

Clinical predictors of treatment outcome in North Indian patients on antiepileptic drug therapy: A prospective observational study.

Neurol India 2018 Jul-Aug;66(4):1052-1059

Institute of Genomics and Integrative Biology (IGIB), New Delhi, India.

Background: Nearly 40%-50% of the individuals fail to respond to first line antiepileptic drug (AED) monotherapy and 30% are refractory, which calls for the need to recognize predictive markers for treatment failure. This study aims to identify clinical factors predictive of a poor prognosis in patients on AED therapy.

Materials And Methods: A prospective follow-up study involving 1056 patients with epilepsy (PWE) aged 5-67 years from North India on phenytoin (PHT, n = 247), carbamazepine (CBZ, n = 369), valproate (VA, n = 271), phenobarbital (PB, n = 50), and multitherapy (MultiT, n = 119) was conducted between 2005 and 2015. Seizure and epilepsy types were diagnosed based on the classifications by the International League Against Epilepsy (ILAE). Patients remaining seizure-free during the past 1 year were assigned to the "no seizure" group and patients experiencing seizure recurrence were assigned to the "recurrent seizures" group.

Results: Of the total, 786 (74.4%) patients were successfully followed up with 60% achieving 1-year seizure remission. Seizure recurrence was observed in the remaining 40% of the patients with a high likelihood in patients with the disease onset at ≤5 years of age [55% vs. 38%, P = 0.0016, odds ratio (OR) = 2.02 (95% confidence interval (CI) = 1.31-3.13)], in patients with cryptogenic epilepsy than with idiopathic/symptomatic epilepsy (48% vs. 32%, P = 0.0049, OR = 1.61 [95% CI = 1.16-2.24]), and in patients with pretreatment seizure frequency ≥12/year (46% vs. 27%, P < 0.0001, OR = 2.21 [95% CI = 1.61-3.05]). Logistic regression analysis also revealed a significant association of seizure recurrence (P < 0.05) with the three variables.

Conclusion: Our findings suggest that an early disease onset, cryptogenic epilepsy, and a higher pretreatment seizure frequency are related to a poor prognosis or poor remission in people with epilepsy (PWE) on AED therapy.
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http://dx.doi.org/10.4103/0028-3886.237000DOI Listing
September 2019

Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis.

PLoS Med 2018 07 11;15(7):e1002591. Epub 2018 Jul 11.

Division of Global HIV and TB, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

Background: An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children.

Methods And Findings: To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%-19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%-48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15-20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0-8.3, p = 0.041 and aOR 5.9, 95% CI 1.7-20.5, p = 0.007, respectively). These findings for high-dose isoniazid may have been affected by site effect, as the majority of patients came from Cape Town. Limitations of this study include the difficulty of estimating the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician's perception of illness, with resulting potential for bias.

Conclusions: This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated.
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http://dx.doi.org/10.1371/journal.pmed.1002591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040687PMC
July 2018
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