Publications by authors named "Subodh Kumar"

417 Publications

Vegetation health conditions assessment and mapping using AVIRIS-NG hyperspectral and field spectroscopy data for -environmental impact assessment in coal mining sites.

Ecotoxicol Environ Saf 2022 May 20;239:113650. Epub 2022 May 20.

National Remote Sensing Centre (NRSC), ISRO, Hyderabad, India.

This paper focuses on vegetation health conditions (VHC) assessment and mapping using high resolution airborne hyperspectral AVIRIS-NG imagery and validated with field spectroscopy-based vegetation spectral data. It also quantified the effect of mining on vegetation health for geo-environmental impact assessment at a fine level scale. In this study, we have developed and modified vegetation indices (VIs) based model for VHC assessment and mapping in coal mining sites. We have used thirty narrow banded VIs based on the statistical measurement for suitable VIs identification. The highest Pearson's r, R, lowest RMSE, and P values indices have been used for VIs combined pixels analysis. The highest different (Healthy vs. unhealthy) vegetation combination index (VCI) has been selected for VHC assessment and mapping. We have also compared VIs model-based VHC results to ENVI (software) forest health tool and Spectral-based SAM classification results. The 1st VCI result showed the highest difference (72.07%) from other VCI. The AUC values of the ROC curve have shown a better fit for the VIs model (0.79) than Spectral classification (0.74), and ENVI FHT (0.68) based on VHC results. The VHC results showed that unhealthy vegetation classes are located at low distances from mine sites, and healthy vegetation classes are situated at high distances. It is also seen that there is a highly significant positive relationship (R =0.70) between VHC classes and distance from mines. These results will provide a guideline for geo-environmental impact assessment in coal mining sites.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113650DOI Listing
May 2022

A preliminary study to evaluate the behavior of Indian population toward E-pharmacy.

Indian J Pharmacol 2022 Mar-Apr;54(2):131-137

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

The use of the Internet has increased exponentially for buying as well as selling of goods. Even the purchase of medications online is no exception. Owing to its benefits, there are certain risk factors in purchase of online medicines. Currently, the data on the use of Internet pharmacies are limited. Thus, the main objective of our study is to assess the knowledge, attitude, and practices (KAP) of Indian population toward E-pharmacy in India carried out in the Department of Pharmacology, PGIMER, Chandigarh. A KAP questionnaire was prepared which was distributed to the participants through Google Forms and a URL sent to them. This questionnaire was divided into four sections including demographics, occupation, income, and use of the Internet to measure the alertness toward the online purchase of medicines. A total of 322 responses were collected, out of which only 268 (83.2%) participants were aware of online pharmacy. The awareness was more in males and that too in urban population. Among the respondents, majority of the users prefer to buy medicines offline (81%, n = 217) which can be due to poor quality of medicines and lack of trustworthy websites. The utmost reason for buying the medicine online was deficiency of availability in the market and differences in the prices. The most preferred drugs respondents were willing to buy online were prescription drugs followed by cosmetics and dietary supplements. In conclusion, of our results, most of the people use the Internet to search for the medications online who prefer to consult the physicians before buying. Therefore, the future of online pharmacy can be improved if there will be some set guidelines, awareness, and knowledge among the users.
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http://dx.doi.org/10.4103/ijp.ijp_836_21DOI Listing
May 2022

Genetic Diversity and Population Structure Reveal Cryptic Genetic Variation and Long Distance Migration of f. sp. in the Indian Subcontinent.

Front Microbiol 2022 13;13:842106. Epub 2022 Apr 13.

ICAR-Indian Institute of Wheat and Barley Research, Regional Station, Shimla, India.

Stem rust caused by f. sp. () is a devastating disease of wheat worldwide since time immemorial. Several wheat stem rust outbreaks have been reported worldwide including India. Approximately 7 mha wheat area in central and peninsular India is highly vulnerable to stem rust epidemics. In this study, a repository of 29 single genotype uredospore pathotypes, representing five geographical regions, was characterized by investigating their virulence phenotype and simple sequence repeat (SSR) genotypes using 37 reproducible polymorphic SSR markers, 32 of which had ≥ 0.50 polymorphic information content (PIC) value. Virulence phenotypes were used to evaluate the virulence frequency (VF) and construct a hypothetical evolutionary hierarchy of these pathotypes. We projected seven lineages to explain the evolutionary pattern of the population. The VF of these pathotypes ranged between 0% and 100%. The virulence-based neighbor-joining (NJ) cluster analysis grouped pathotypes into five virulence groups. Likewise, five molecular groups were categorized using molecular genotypes. The molecular grouping was supported by principal coordinate analysis (PCoA), which revealed 25% of the cumulative variance contributed by the first two axes. Analysis of molecular variance (AMOVA) revealed 8 and 92% of the variation among and within the populations, respectively. The Mantel test confirmed a positive but weak correlation ( = 0.15) between virulence phenotypes and SSR genotypes. The highest and lowest values of different genetic diversity parameters (Na, Ne, I, He, uHe, and %P) revealed maximum and minimum variability in the population from Maharashtra and Uttar Pradesh, respectively. The population structure analysis clustered 29 pathotypes into two subpopulations and an admixture. Our results demonstrated that there was significant genetic diversity among pathotypes resulting from their long-distance dispersal ability complemented by gene flow. These findings provide insights into the virulence patterns, genetic variations, and possible evolution of pathotypes, which would support strategic stem rust resistance breeding.
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http://dx.doi.org/10.3389/fmicb.2022.842106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044083PMC
April 2022

Imaging in extremity vascular trauma: can MDCT angiography predict the nature of injury?

Emerg Radiol 2022 Apr 25. Epub 2022 Apr 25.

Department of Surgical Disciplines, Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India.

Objective: This study aims to evaluate the utility of computed tomography angiography (CTA) signs of vascular injury in the differentiation of vessel transection from pure thrombosis with intact vessel wall.

Methods: Retrospective analysis was done on 146 consecutive patients who had undergone CTA and surgical exploration from January 2015 to September 2019. Twelve imaging parameters were assessed. Chi-square was used to test the difference between groups. In addition, a scoring system was devised where one point each was added for the presence of 5 signs and absence of 3 signs. ROC analysis was done for the variables which had shown significant difference between groups and for the composite score.

Results: On surgical exploration, 87 patients had transection of vessel, while 59 had thrombosis. Significant difference was found among the two groups in non-opacification, pseudoaneurysm, extravasation (p = 0.04 each), thrombosed cord (p < 0.001), collaterals (p = 0.001) and hematoma (p = 0.002), while other signs did not show significant difference. The AUC value for each of these variables was < 0.650, while for the score, AUC was .843(.773-.913). A cut-off value of ≥ 1.5 gave 83.1% sensitivity and 70% specificity for diagnosing transection.

Conclusion: CTA is a useful tool to classify the nature of vascular injury. It is advisable to use a composite score for maximum diagnostic value.
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http://dx.doi.org/10.1007/s10140-022-02050-4DOI Listing
April 2022

Multi-locus genome-wide association studies (ML-GWAS) reveal novel genomic regions associated with seedling and adult plant stage leaf rust resistance in bread wheat (Triticum aestivum L.).

Heredity (Edinb) 2022 Apr 13. Epub 2022 Apr 13.

ICAR-National Bureau of Plant Genetic Resources, New Delhi, 110012, India.

Leaf rust is one of the important diseases limiting global wheat production and productivity. To identify quantitative trait nucleotides (QTNs) or genomic regions associated with seedling and adult plant leaf rust resistance, multilocus genome-wide association studies (ML-GWAS) were performed on a panel of 400 diverse wheat genotypes using 35 K single-nucleotide polymorphism (SNP) genotyping assays and trait data of leaf rust resistance. Association analyses using six multi-locus GWAS models revealed a set of 201 significantly associated QTNs for seedling and 65 QTNs for adult plant resistance (APR), explaining 1.98-31.72% of the phenotypic variation for leaf rust. Among these QTNs, 51 reliable QTNs for seedling and 15 QTNs for APR were consistently detected in at least two GWAS models and were considered reliable QTNs. Three genomic regions were pleiotropic, each controlling two to three pathotype-specific seedling resistances to leaf rust. We also identified candidate genes, such as leucine-rich repeat receptor-like (LRR) protein kinases, P-loop containing nucleoside triphosphate hydrolase and serine-threonine/tyrosine-protein kinases (STPK), which have a role in pathogen recognition and disease resistance linked to the significantly associated genomic regions. The QTNs identified in this study can prove useful in wheat molecular breeding programs aimed at enhancing resistance to leaf rust and developing next-generation leaf rust-resistant varieties.
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http://dx.doi.org/10.1038/s41437-022-00525-1DOI Listing
April 2022

Comparison of extended totally extra peritoneal (eTEP) vs intra peritoneal onlay mesh (IPOM) repair for management of primary and incisional hernia in terms of early outcomes and cost effectiveness-a randomized controlled trial.

Surg Endosc 2022 Mar 11. Epub 2022 Mar 11.

Department of Surgical Disciplines, All India Institute of Medical Sciences, Room No. 5026A, 5th Floor, Teaching Block, Ansari Nagar, New Delhi, 110029, India.

Background: There are no randomized controlled trials comparing the eTEP with IPOM repair and this randomized study was designed to compare the two techniques in terms of early pain, cost effectiveness, and quality of life.

Method: This was a prospective randomized trial with intention to treat analysis. The primary outcome was immediate post-operative pain scores. Operative time, conversions, peri operative morbidity, hospital stay, return to daily activities, incremental cost effectiveness ratio and quality of life (WHO-QOL BREF) were secondary outcomes.

Results: Sixty patients were randomized equally. Early post-operative pain scores and seroma rates were significantly lower and with a significantly earlier return to activity in eTEP group (p value < 0.05). With negative costs and positive effects, eTEP group was 2.4 times more cost effective.

Conclusion: eTEP repair is better in terms of lesser early post-operative pain, earlier return to activities and cost effectiveness in small and medium size defects.
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http://dx.doi.org/10.1007/s00464-022-09180-3DOI Listing
March 2022

Pharmacokinetics-Based Optimization of Phototherapy in Neonates Undergoing Treatment for Hyperbilirubinemia.

Maedica (Bucur) 2021 Dec;16(4):603-608

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.

Neonatal jaundice results from combined effects of both increased production of bilirubin and decreased hepatic excretory capacity in neonates. Since its discovery, phototherapy is the most widespread treatment used in neonatal jaundice. In this work, we try to search for a relationship between exposure to phototherapy and decrease in serum bilirubin (linearity vs proportionality). The present research was non-randomized prospective study conducted in the Neonatal Intensive Care Unit (NICU), Department of Paediatrics, AIIMS, New Delhi, and the Department of Pharmacology, AIIMS, New Delhi, India. Subjects were recruited from neonates admitted in NICU AIIMS, which meets our selection criteria. Infants were given a low dose of either phototherapy continuously or phototherapy for the first six hours and a double dose of phototherapy for the next six hours. Samples were collected before the beginning of the study (0 hours) and then at six and 12 hours. Bilirubin concentration was measured using HPLC and (LC-MS/MS). The percentage of reduction during the 6-12-hour interval was compared with that during the 0-6-hour interval if all experimental conditions were kept unchanged. A relationship curve between percentage of reduction and irradiance was created based on the percentage of reduction in serum bilirubin during the 0-6-hour and 0-12-hour intervals. The present study suggests that the relationship between efficacy, as measured by percentage of reduction in serum bilirubin, and irradiance is unlikely to be linear. Collected data are insufficient to clearly distinguish between proportionality and saturation point, considering that the results may be possible with both of these hypotheses.
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http://dx.doi.org/10.26574/maedica.2021.16.4.603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897802PMC
December 2021

Early Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer's Disease.

Cells 2022 02 19;11(4). Epub 2022 Feb 19.

Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

The purpose of our study is to investigate early cellular, molecular, morphological and behavioral changes in humanized amyloid-beta-knock-in (hAbKI) mice. Using seven-month-old homozygous hAbKI mice, we studied behavioral phenotype parameters, including spatial learning and memory (Morris Water Maze), locomotor activity (open field), working memory (Y-maze) and motor coordination (rotarod); mRNA abundance, protein levels, soluble amyloid-beta 40 and 42 levels and regional immunoreactivities of key markers of mitochondrial dynamics, mitochondrial biogenesis, synaptic health, mitophagy and autophagy; mitochondrial function and using transmission electron microscopy & Golgi-Cox staining, we assessed mitochondrial morphology and dendritic spines. Our extensive behavioral analysis revealed that seven-month-old hAbKI mice showed impairments in motor coordination, reduced locomotor and exploration activities, impairments in working memory and spatial learning and memory. Our mRNA and protein analyses revealed the increased expression of mitochondrial-fission genes and reduced expression of mitochondrial-fusion, mitochondrial-biogenesis, synaptic, autophagy and mitophagy genes in seven-month-old hAbKI mice. An immunofluorescence analysis revealed altered immunoreactivities and agreed with the immunoblot results. Transmission-electron-microscopy data revealed increased mitochondrial fragmentation and reduced mitochondrial length in both hippocampal and cortical tissues of seven-month-old hAbKI mice and mitochondrial function defective. A Golgi-Cox-staining analysis revealed reduced dendritic spines in both cerebral cortices and hippocampi of hAbKI mice. Soluble amyloid-beta (1-40 and 1-42) were detected in three-month-old hAbKI mice and progressively increased in seven-month-old mice. These observations suggest that the human amyloid-beta peptide is sufficient to cause behavioral, mitochondrial, synaptic and ultrastructural changes in seven-month-old hAbKI mice. Our study findings also suggest that hAbKI mice might serve as a model for preclinical studies of preventive therapies.
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http://dx.doi.org/10.3390/cells11040733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869866PMC
February 2022

A Chromo-Fluorogenic Naphthoquinolinedione-Based Probe for Dual Detection of Cu and Its Use for Various Water Samples.

Molecules 2022 Jan 25;27(3). Epub 2022 Jan 25.

Department of Bionano Engineering, Hanyang University, Ansan 15588, Korea.

The presence of an abnormal amount of Cu in the human body causes various health issues. In the current study, we synthesized a new naphthoquinolinedione-based probe (probe ) to monitor Cu in different water systems, such as tap water, lakes, and drain water. Two triazole units were introduced into the probe via a click reaction to increase the binding affinity to a metal ion. In day-light, probe dissolved in a mixed solvent system (HEPES: EtOH = 1:4) showed a vivid color change from light greenish-yellow to pink in the presence of only Cu among various metal ions. In addition, the green luminescence and fluorescence emission of the probe were effectively bleached out immediately after Cu addition. The limit of detection (LOD) of the probe was 0.5 µM when a ratio-metric method was used for metal ion detection. The fluorescence titration data of the probe with Cu showed a calculated LOD of 41.5 pM. Hence, probe possesses the following dual response toward Cu detection: color change and fluorescence quenching. Probe was also useful for detecting Cu spiked in tap/lake water as well as the cytoplasm of live HeLa cells. The current system was investigated using ultraviolet-visible and fluorescence spectroscopy as well as density functional theory calculations (DFT).
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http://dx.doi.org/10.3390/molecules27030785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838320PMC
January 2022

Detection of nucleotide variants in FCGRT (Fc fragment of IgG, receptor, transporter, alpha) gene and their influence on colostral IgG concentration in Indian water buffalo (Bubalus bubalis).

Mol Biol Rep 2022 Feb 13. Epub 2022 Feb 13.

Division of Animal Genetics, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, India.

Background: The neonatal Fc receptors (FcRn) mediate the transfer of immunoglobulin G (IgG) molecules from a dam's circulation to the colostrum produced by it immediately after parturition. In ruminants, the calves born are agammaglobulinemic therefore, ingestion of colostrum with high concentration of IgG imparts passive immunity to the newborn. The FcRn molecule is a heterodimer, coded by FCGRT (Fc fragment of IgG Receptor Transporter neonatal) and B2M (Beta 2 microglobulin) genes. Present study attempted to identify single nucleotide polymorphisms (SNPs) in the FCGRT gene in 40 buffaloes of Murrah breed and evaluated the association of these nucleotide variations and haplotypes with IgG concentration in their colostrum.

Methods And Results: Animals producing colostrum with high IgG and low IgG levels were identified by indirect ELISA and selected. SNPs were detected in the FCGRT gene sequence of selected animals by amplifying it in nine fragments covering all exons (with flanking introns) followed by PCR-single strand conformational polymorphism (PCR-SSCP). A total of nine SNPs were observed of which seven were present in flanking introns and two in exon 4 of the gene. The SNP A75G was non-synonymous and produced an amino acid change from isoleucine to valine. The exonic SNPs and corresponding haplotypes were found to be significantly (P < 0.01 and 0.05 respectively) associated with colostral IgG concentration based on Odds ratios at 95% confidence interval.

Conclusion: Polymorphism in FCGRT gene is found to be associated with IgG concentration in colostrum and identification of females with desirable variations may prevent failure of passive transfer in neonatal ruminants.
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http://dx.doi.org/10.1007/s11033-022-07217-3DOI Listing
February 2022

CT findings in renovascular injuries following abdominal trauma: a pictorial review.

Emerg Radiol 2022 Jun 5;29(3):595-604. Epub 2022 Feb 5.

Division of Trauma Surgery and Critical Care, Jai Prakash Narayana Apex Trauma Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Renal vascular injuries are more devastating than parenchymal injuries alone, thus account for higher injury grade and require prompt recognition. Revised AAST organ injury scale (OIS) for renal trauma has incorporated CT-diagnosed vascular injuries into renal injury grading which includes pseudoaneurysm and arteriovenous fistula, along with addition of some new descriptors of renovascular injury. Dual-phase contrast-enhanced CT (with both arterial and venous phase) can easily pick up renovascular injuries and is the modality of choice for imaging renovascular trauma. Radiologist should be well versed with the imaging findings of renovascular injuries so that accurate injury grading can be done and further management can be planned at the earliest.
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http://dx.doi.org/10.1007/s10140-022-02027-3DOI Listing
June 2022

Epigenetics of wheat-rust interaction: an update.

Planta 2022 Jan 27;255(2):50. Epub 2022 Jan 27.

ICAR-Indian Institute of Wheat and Barley Research, Regional Station, Shimla, Himachal Pradesh, 171002, India.

Main Conclusion: The outcome of different host-pathogen interactions is influenced by both genetic and epigenetic systems, which determine the response of plants to pathogens and vice versa. This review highlights key molecular mechanisms and conceptual advances involved in epigenetic research and the progress made in epigenetics of wheat-rust interactions. Epigenetics implies the heritable changes in the way of gene expression as a consequence of the modification of DNA bases, histone proteins, and/or non-coding-RNA biogenesis without disturbing the underlying nucleotide sequence. The changes occurring between DNA and its surrounding chromatin without altering its DNA sequence and leading to significant changes in the genome of any organism are called epigenetic changes. Epigenetics has already been used successfully to explain the mechanism of human pathogens and in the identification of pathogen-induced modifications within various host plants. Wheat rusts are one of the most vital fungal diseases throughout the major wheat-growing areas of the world. The epigenome in plant pathogens causing diseases such as wheat rusts is mysterious. The investigations of host and pathogen epigenetics in the wheat rusts system can offer a piece of suitable evidence for elucidation of the molecular basis of host-pathogen interaction. Besides, the information on the epigenetic regulation of the genes involved in resistance or pathogenicity will provide better insights into the complex resistance signaling pathways and could provide answers to certain key questions, such as whether epigenetic regulation of certain genes is imparting resistance to host in response of certain pathogen elicitors or not. In the last few years, there has been an upsurge in research on the host as well as pathogen epigenetics and its outcome in plant-pathogen interactions. This review summarizes the progress made in the areas related to the epigenetic control of host-pathogen interaction with particular emphasis on wheat rusts.
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http://dx.doi.org/10.1007/s00425-022-03829-yDOI Listing
January 2022

Elucidating the population structure and genetic diversity of Indian Puccinia striiformis f. sp. tritici pathotypes based on microsatellite markers.

Phytopathology 2022 Jan 20. Epub 2022 Jan 20.

ICAR - Indian Institute of Wheat and Barley Research, 54642, Karnal, Haryana, India;

In India, systematic wheat yellow rust survey and pathotype (race) analysis work began in 1930. However, the information on population structure and genetic diversity of yellow rust pathogen is not available. We conducted studies on population structure and genetic diversity of f. sp. ( pathotypes using 38 simple sequence repeat (38 SSR) primer-pairs. Bayesian assignment and discriminant analysis of principal components (DAPC) indicated the presence of two distinct Pst sub-populations (Pop1 and Pop2) along with 37.9% admixed pathotypes. The unweighted pair-group method with arithmetic mean (UPGMA) also categorized these pathotypes into two major clusters. Principal coordinates analysis (PCoA) explained 20.06% and 12.50% variance in horizontal and vertical coordinates, respectively. Index of association (I) and the standardized index of association (̅) showed that Pst sub-populations reproduced asexually (clonally). In total, 102 alleles were detected, the expected heterozygosity (Hexp) per locus ranged from 0.13 to 0.73, with a mean of 0.47. The average polymorphic information content (PIC) value of 0.40 indicated high genetic diversity among pathotypes. Analysis of molecular variance (AMOVA) revealed 12% of the total variance between sub-populations, 11% among the pathotypes of each sub-population, and 77% within pathotypes. A significant moderate level of genetic differentiation (Fst = 0.122, p < 0.001) and gene flow (Nm = 1.80) were observed between sub-populations. The Pst virulence phenotypes showed a weak positive correlation (R2 = 0.027, p < 0.02) with molecular genotypes.
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http://dx.doi.org/10.1094/PHYTO-10-21-0422-RDOI Listing
January 2022

Getting Access to the COVID-19 Vaccine: What Should Be Our Approach?

J Pharm Bioallied Sci 2021 Jul-Sep;13(3):331-332. Epub 2021 Nov 24.

Department of Pharmacology, AIIMS Deoghar, Deoghar, Jharkhand, India.

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http://dx.doi.org/10.4103/jpbs.JPBS_521_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698079PMC
November 2021

A Case of Recurrent Right-Sided Loculated Pleural Effusion With Right Psoas Abscess.

Cureus 2021 Nov 29;13(11):e20022. Epub 2021 Nov 29.

Radiotherapy, All India Institute of Medical Sciences (AIIMS) Gorakhpur, Gorakhpur, IND.

Tuberculous psoas abscess is a rare entity and is mostly associated with tuberculosis of the spine in view of the close vicinity. It is mostly secondary to direct extension from adjacent structures. Here we present a case of a young man who presented to us with a persistent swelling in the right side of the back and with a history of taking anti-tubercular drugs for six months. He was finally diagnosed with a recurrent right-sided loculated pleural effusion with a right-sided psoas abscess. Surgical drainage of the psoas abscess was done and he was again started on anti-tubercular therapy (ATT).
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http://dx.doi.org/10.7759/cureus.20022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716128PMC
November 2021

COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis, and meta-regression analysis.

Indian J Pharmacol 2021 Nov-Dec;53(6):499-510

Department of Pharmacology, PGIMER, Chandigarh, India.

Background: Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19-associated rhino-orbito-cerebral mucormycosis (C-ROCM) cases.

Materials And Methods: Eight literature databases were screened using appropriate keywords from November 1, 2019, to June 30, 2021. The objectives were to analyze the clinical and microbiological profile, risk factor/comorbidity, intervention, and outcome. "R-metafor package" was used for analysis.

Results: A total of 23 studies were included. The mean age of presentation of C-ROCM was 54.6 years. The most common presentation was ptosis (72.7%), lid edema (60.6%), proptosis (60.6%), ophthalmoplegia (57.3%), loss of vision (53.7%), facial edema (34.7%), and nasal-blockage (11.8%). Evidence of intracranial spread was seen in 42.8% of cases. Rhizopus was the most common fungus (57.1%) isolated in fungal culture. Among C-ROCM patients, diabetes was the commonest comorbid condition, and the use of corticosteroids related to COVID-19 treatment was the most common risk factor (85.75%). Compared to controlled diabetics, C-ROCM was significantly higher among uncontrolled diabetics (odds ratio [OR] 0.15, 95% confidence interval [C.I.] 0.041-0.544, P = 0.0010). However, no significant association was seen between C-ROCM and COVID-19 severity (OR 0.930, 95% C.I. 0.212-4.087, P = 0.923). For treatment, amphotericin-B was the most common antifungal drug used which was followed by surgical options. However, mortality was high (prevalence 0.344, 95% C.I. 0.205-0.403) despite treatment.

Conclusion: Although local rhino-orbito symptoms were the first to appear, rapid intracranial extension was seen in a significant number of C-ROCM cases. Uncontrolled diabetes and excessive use of corticosteroid were the most common risk factors present among the C-ROCM cases. High index clinical suspicion is imperative (specifically among COVID-19 patients with diabetes), and routine screening may be helpful.
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http://dx.doi.org/10.4103/ijp.ijp_839_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764981PMC
January 2022

Prevalence and pattern of geriatric emergencies in a teaching hospital of North India.

J Family Med Prim Care 2021 Oct 5;10(10):3899-3903. Epub 2021 Nov 5.

Department of Emergency Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Introduction: Changing demographic patterns worldwide and improvement in healthcarehas contributed to increasing visits to the emergency department byelderly patients. Geriatric patients usually have multiple co-morbidities and declining physiological functional status. This complex interplay of various factors requires a specific and curated approach from the emergency physicians. Our aim was to study the pattern and prevalence of geriatric emergencies and the profile of infectious and non-infectious causes of fever in geriatric population in our tertiary care center.

Materials And Methods: This retrospective descriptive study was carried out at a tertiary care hospital of north India and included all patients aged more than 18 years who visited the emergency department over a period of six months (July 2018 to December 2018). Detailed data regarding demographic, clinical and diagnosis was obtained retrospectively from the hospital records system. The patients were divided into two groups, age less than 60 years and elderly patients more than 60 years of age for comparison.

Results: A total of 24768 patients above the age of 18 years visited the emergency department over a period of six months. Out of which 5399 (27.5%) patients belonged to the geriatric age group more than 60 years of age. 2474 (45.8%) geriatric age group patientswere triaged to critical areas level one and level two as compared to 4668 (24.1%) patients aged less than 60 years. Ninety (1.8%) geriatric patients succumbed to death as compared to 77 (0.4%) patients aged less than 60 years. 651 (21.9%) geriatric patients were shifted to intensive care unit as opposed to 1038 (14.8%) patients of the younger age group.226 (4.2%) geriatric patients presented with fever in the emergency department.116 (73.4%) patients having underlying co-morbidities , had fever due to infectious causes whereas 42 ( 26.5%) patients had fever due to non-infectious causes.

Conclusion: The clinical presentation mortality and morbidity pattern of geriatric patients differs significantly from that of younger population and requires a customized approach and dedicated emergency setups.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_2450_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653474PMC
October 2021

Students' Perception on Online Teaching and Learning during COVID-19 Pandemic in Medical Education.

Maedica (Bucur) 2021 Sep;16(3):439-444

Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Deoghar, India.

The COVID-19 pandemic has changed the method of learning in medical education and forced us to switch over to the online mode of learning. The aim of the present study was to assess students' opinion on online learning in the time of COVID-19. This is a descriptive cross-sectional questionnaire-based study conducted among undergraduate medical students. The closed, open-ended and validated questionnaires were administered to students to get feedback on utility, feasibility, suitability, effectiveness online learning as well as problems faced during e-learning and suggested solutions to them. About 62.7% of undergraduates had internet access. Sixty seven percent of undergraduates were willing to actively communicate with their classmates and instructors electronically, whereas 64.9% of students were communicating online comfortably. Also, 82.20% of students were able to clear their doubt from teacher whenever required. Only 38 (20.5%) of students had equated online learning from home to conventional lectures in a lecture hall. However, 28.6% of students felt comfortable to learn from home in the pandemic era. Students (66.5%) wanted proper breaks, which would enable them to get sufficient time to think about the topic and frame their questions to clear their doubts. About 80% of students wanted that a sufficient number of questions should be asked to transform online learning sessions into interactive approaches. They highlighted distractions during online learning at home, problems of network accessibility, connectivity, lack of synchrony between audio and video, and audio disturbance. More than half of our students prefer classroom learning because it facilitates better teacher-student interactions, stimulates understanding, provides a distraction-free environment, and permits an appropriate pace of learning, encouraging interactivity and independence from technology.
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http://dx.doi.org/10.26574/maedica.2021.16.3.439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643544PMC
September 2021

Blunt Trauma to Brachiocephalic Artery: Presentation and Management.

Am Surg 2021 Dec 1:31348211056265. Epub 2021 Dec 1.

Division of Trauma Surgery and Critical Care, Jai Prakash Narayan Apex Trauma Centre (JPNATC), 28730All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Isolated innominate artery injury is very rare and accounts for less than 3% of recognized arterial injuries. Surgical exploration of the artery, especially at the origin of the artery from the arch of the aorta, is surgically challenging. Due to its rarity, any 1 surgeon's experience in dealing with innominate artery injury is bound to be limited. We report 2 cases of innominate artery injury post-blunt chest trauma. Both patients underwent thoracotomy and innominate artery Dacron graft repair and both had an uneventful postoperative course.
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http://dx.doi.org/10.1177/00031348211056265DOI Listing
December 2021

Deregulated mitochondrial microRNAs in Alzheimer's disease: Focus on synapse and mitochondria.

Ageing Res Rev 2022 01 20;73:101529. Epub 2021 Nov 20.

Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Electronic address:

Alzheimer's disease (AD) is the most common cause of dementia and is currently one of the biggest public health concerns in the world. Mitochondrial dysfunction in neurons is one of the major hallmarks of AD. Emerging evidence suggests that mitochondrial miRNAs potentially play important roles in the mitochondrial dysfunctions, focusing on synapse in AD progression. In this meta-analysis paper, a comprehensive literature review was conducted to identify and discuss the (1) role of mitochondrial miRNAs that regulate mitochondrial and synaptic functions; (2) the role of various factors such as mitochondrial dynamics, biogenesis, calcium signaling, biological sex, and aging on synapse and mitochondrial function; (3) how synapse damage and mitochondrial dysfunctions contribute to AD; (4) the structure and function of synapse and mitochondria in the disease process; (5) latest research developments in synapse and mitochondria in healthy and disease states; and (6) therapeutic strategies that improve synaptic and mitochondrial functions in AD. Specifically, we discussed how differences in the expression of mitochondrial miRNAs affect ATP production, oxidative stress, mitophagy, bioenergetics, mitochondrial dynamics, synaptic activity, synaptic plasticity, neurotransmission, and synaptotoxicity in neurons observed during AD. However, more research is needed to confirm the locations and roles of individual mitochondrial miRNAs in the development of AD.
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http://dx.doi.org/10.1016/j.arr.2021.101529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692431PMC
January 2022

Serum ferritin as a predictive biomarker in COVID-19. A systematic review, meta-analysis and meta-regression analysis.

J Crit Care 2022 02 20;67:172-181. Epub 2021 Nov 20.

Department of Biochemistry, AIIMS Rishikesh, India. Electronic address:

Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis evaluates serum ferritin level in different severity levels in COVID-19. Studies evaluating serum ferritin level in different clinical contexts (COVID-19 vs. control, mild to moderate vs. severe to critical, non-survivor vs. survivor, organ involvement, ICU and mechanical ventilation requirement) were included (total 9 literature databases searched). Metaanalysis and metaregression was carried out using metaphor "R" package. Compared to control (COVID-19 negative), higher ferritin levels were found among the COVID-19 patients [SMD -0.889 (95% C.I. -1.201, -0.577), I = 85%]. Severe to critical COVID-19 patients showed higher ferritin levels compared to mild to moderate COVID-19 patients [SMD 0.882 (0.738, 1.026), I = 85%]. In meta-regression, high heterogeneity was observed could be attributed to difference in "mean age", and "percentage of population with concomitant co-morbidities". Non-survivors had higher serum ferritin level compared to survivors [SMD 0.992 (0.672, 1.172), I = 92.33%]. In meta-regression, high heterogeneity observed could be attributed to difference in "mean age" and "percentage of male sex". Patients requiring ICU [SMD 0.674 (0.515 to 0.833), I = 80%] and mechanical ventilation [SMD 0.430 (0.258, 0.602), I = 32%] had higher serum ferritin levels compared to those who didn't. To conclude, serum ferritin level may serve as an important biomarker which can aid in COVID-19 management. However, presence of other co-morbid conditions/confounders warrants cautious interpretation.
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http://dx.doi.org/10.1016/j.jcrc.2021.09.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604557PMC
February 2022

A Rare Case of Sternoclavicular Tuberculosis Diagnosed Using Microchip-Based Polymerase Chain Reaction in a Diabetic Female.

Cureus 2021 Oct 17;13(10):e18845. Epub 2021 Oct 17.

Pulmonary Medicine, All India Institute of Medical Science Gorakhpur, Gorakhpur, IND.

Osteoarticular tuberculosis (TB) accounts for almost 10% of all extrapulmonary TB cases. In the majority of cases, the spine, knee, hip, and large bones are involved; other sites like the sternoclavicular joint, elbow, wrist, and smaller joints are infrequently involved. Uncommon locations of extrapulmonary TB pose a challenge in diagnosis due to lack of clinical suspicion, non-availability of samples, and unavailability of suitable diagnostic modalities. Here we report a case of uncommon location of osteoarticular TB diagnosed through microchip-based real-time polymerase chain reaction (PCR).
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http://dx.doi.org/10.7759/cureus.18845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597680PMC
October 2021

Therapeutics effect of mesenchymal stromal cells in reactive oxygen species-induced damages.

Hum Cell 2022 Jan 20;35(1):37-50. Epub 2021 Nov 20.

Stem Cell & Gene Therapy Research Group, Institute of Nuclear Medicine & Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi, 110054, India.

Reactive Oxygen Species are chemically unstable molecules generated during aerobic respiration, especially in the electron transport chain. ROS are involved in various biological functions; any imbalance in their standard level results in severe damage, for instance, oxidative damage, inflammation in a cellular system, and cancer. Oxidative damage activates signaling pathways, which result in cell proliferation, oncogenesis, and metastasis. Since the last few decades, mesenchymal stromal cells have been explored as therapeutic agents against various pathologies, such as cardiovascular diseases, acute and chronic kidney disease, neurodegenerative diseases, macular degeneration, and biliary diseases. Recently, the research community has begun developing several anti-tumor drugs, but these therapeutic drugs are ineffective. In this present review, we would like to emphasize MSCs-based targeted therapy against pathologies induced by ROS as cells possess regenerative potential, immunomodulation, and migratory capacity. We have also focused on how MSCs can be used as next-generation drugs with no side effects.
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http://dx.doi.org/10.1007/s13577-021-00646-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605474PMC
January 2022

MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease.

Redox Biol 2021 Nov 9;48:102182. Epub 2021 Nov 9.

Internal Medicine Department, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Neuroscience & Pharmacology, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Neurology Departments School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Electronic address:

Background: MicroRNA-455-3p is one of the highly conserved miRNAs involved in multiple cellular functions in humans and we explored its relevance to learning and memory functions in Alzheimer's disease (AD). Our recent in vitro studies exhibited the protective role of miR-455-3p against AD toxicities in reducing full-length APP and amyloid-β (Aβ) levels, and also in reducing defective mitochondrial biogenesis, impaired mitochondrial dynamics and synaptic deficiencies. In the current study, we sought to determine the function of miR-455-3p in mouse models.

Methods: For the first time we generated both transgenic (TG) and knockout (KO) mouse models of miR-455-3p. We determined the lifespan extension, cognitive function, mitochondrial biogenesis, mitochondrial dynamics, mitochondrial morphology, dendritic spine density, synapse numbers and synaptic activity in miR-455-3p TG and KO mice.

Results: MiR-455-3p TG mice lived 5 months longer than wild-type (WT) counterparts, whereas KO mice lived 4 months shorter than WT mice. Morris water maze test showed improved cognitive behavior, spatial learning and memory in miR-455-3p TG mice relative to age-matched WT mice and miR-455-3p KO mice. Further, mitochondrial biogenesis, dynamics and synaptic activities were enhanced in miR-455-3p TG mice, while these were reduced in KO mice. Overall, overexpressed miR-455-3p in mice displayed protective effects, whereas depleted miR-455-3p in mice exhibited deleterious effects in relation to lifespan, cognitive behavior, and mitochondrial and synaptic activities.

Conclusion: Both mouse models could be ideal research tools to understand the molecular basis of aging and its relevance to AD and other age-related diseases.
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http://dx.doi.org/10.1016/j.redox.2021.102182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604688PMC
November 2021

An insight into the simulation directed understanding of the mechanism in SARS CoV-2 N-CTD, dimer integrity, and RNA-binding: Identifying potential antiviral inhibitors.

J Biomol Struct Dyn 2021 Nov 9:1-13. Epub 2021 Nov 9.

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Coronavirus 2019 is a transmissible disease and has caused havoc throughout the world. The present study identifies the novel potential antiviral inhibitors against the nucleocapsid C-terminal domain that aids in RNA-binding and replication. A total of 485,629 compounds were screened, and MD was performed. The trajectory analysis (DCCM & PCA), structural integrity, and degree of compaction depicted the protein-ligand complex stability (PDB-PISA and R). Results obtained from screening shortlists 13 compounds possessing high Docking score. Further, seven compounds had a permissible RMSD limit (3 Å), with robust RMSF. Post-MD analysis of the top two compounds (204 and 502), DCCM & PCA analysis show a positive atomic displacements correlation among residues of active sites-dimer (Chain A and Chain B) & residual clustering. The ΔG of RNA-bound (-83.5 kcal/mol) and drug-bound N-CTD-204 (-40.8 kcal/mol) and 502(-39.7 kcal/mol) as compared to Apo (-35.95 kcal/mol) suggests stabilization of protein, with less RNA-binding possibility. The R values depict the loss of compactness on RNA-binding when compared to the drug-bound N-CTD complex. Further, overlapping the protein complexes (0 ns and 100 ns) display significant changes in RMSD of the protein (204-2.07 Å and 502-1.89 Å) as compared to the Apo (1.72 Å) and RNA-bound form (1.76 Å), suggesting strong interaction for compound 204 as compared to 502. ADMET profiling indicates that these compounds can be used for further experiments ( and pre-clinical). Compound 204 could be a promising candidate for targeting the N-protein-RNA assembly and viral replication.
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http://dx.doi.org/10.1080/07391102.2021.1996463DOI Listing
November 2021

Yogic Neti-Kriya Using Povidone Iodine: Can it have a Preventive Role Against SARS-CoV-2 Infection Gateway?

Indian J Otolaryngol Head Neck Surg 2021 Oct 17:1-7. Epub 2021 Oct 17.

Department of Pharmacology, PGIMER, Chandigarh, Pin 160012 India.

During this COVID-19 pandemic, except steroid, none of the therapeutic measures have showed any evidence of efficacy. Traditionally jala-neti using lukewarm salted water remains a yogic way of maintaining upper airway hygiene. Saline irrigation decreases the concentration of inflammatory mediators (e.g. histamine, leukotriene etc.) in nasal secretions, reduces the severity and frequency of sinusitis, reduce need of antibiotic therapy and restores competency of nasal mucosa. Jala-neti is an integral part of six cleansing techniques of yogic kriyas practised in India since thousands of years. Jala-neti can clean the upper airways, prevents colonization of infectious agents, removes foreign bodies, prevents stasis of mucous and subsequently enhances the drainage of paranasal sinuses and maintain health. Regular practice of Jala neti improves nasal symptoms and overall health status of patients with sinusitis. Jala-neti sample can even be used for COVID-19 diagnosis. Povidone iodine (PVP-I) has been utilized as a time tested antimicrobial agent with broad spectrum coverage against wide range of bacteria and viruses. Anti-SARS-CoV-2 action of PVP-I was seen at a concentration as low as 0.45% PVP-I is generally well tolerated upto 5%, however nasal ciliotoxicity is reported at this concentration, however, this toxicity is not reported with lower concentrations(1.25% and 0.5%). So, theoretically, by using neti-kriya with povidone iodine (0.5-1%) as irrigation solution can combine and enhance the protection against COVID-19 and this can be an important armor in the fight against COVID-19. However, this hypothesis needs to be validated in real life clinical trial scenario before implementing.
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http://dx.doi.org/10.1007/s12070-021-02885-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520578PMC
October 2021

Effect of Short-term-focused Training on a Phantom Model in Improving Operative Room Performance Among Surgical Residents: A Randomized Trial.

Surg Laparosc Endosc Percutan Tech 2021 Oct 22;32(2):159-165. Epub 2021 Oct 22.

Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, Delhi, India.

Background: Meta-analysis has shown the effectiveness of various training methods for the acquisition of laparoscopic skills in surgical training. However, there is very limited literature focusing on the translation of skill acquisition on training models into improved operating room (OR) performance. This study was conducted to evaluate the effectiveness of the Tuebingen trainer with integrated Porcine tissue in improving OR the performance of surgical trainees using standard assessment tools.

Materials And Methods: The study was a single-blinded double-armed randomized control study conducted between July 2016 and March 2018. Eighteen, fourth, and fifth semesters of surgery residents were included in the study. The baseline performance was assessed in OR by performing laparoscopic cholecystectomy using validated scores, that is, Global Operative Assessment of Laparoscopic Skills (GOALS), Additional Five Criteria, Task-specific Checklist, Error Checklist, Visual Analogue Scale. The residents were then randomized into trainee and nontrainee groups. The training group received 5 days of short-term-focused training on the Tuebingen trainer, and the improvement was reassessed in OR.

Results: The demographic profile of residents was similar. The baseline scores were comparable. The training group showed statistically significant improvement in GOALS (9.88±1.76 to 12±0.66, P=0.05 vs. 10.33±1.5 to 11.4±2.24, P=0.28), task-specific checklist (42.22±10.92 to 53.33±14.14, P=0.027 vs. 45.55±10.13 to 50±17.32, P=0.51), and error checklist. The operating time significantly reduced (36.0±4.03 vs. 50.44±11.39, P=0.0025) following training.

Conclusions: Our study concludes that the training on the Tuebingen trainer with integrated porcine organs results in a statistically significant improvement in the OR performance of surgical residents as compared with the nontrained residents, thereby indicating a transfer of skills from training to OR.
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http://dx.doi.org/10.1097/SLE.0000000000001016DOI Listing
October 2021

Efficacy of Interferon-β in Moderate-to-Severe Hospitalised Cases of COVID-19: A Systematic Review and Meta-analysis.

Clin Drug Investig 2021 Dec 23;41(12):1037-1046. Epub 2021 Oct 23.

All India Institute of Medical Sciences, Deoghar, India.

Background And Objective: Interferon-β, as with several other anti-viral agents, has been investigated as a treatment option for COVID-19 as a repurposed drug. The present study is a systematic review and meta-analysis of interferon-β to determine its efficacy among moderate-to-severe COVID-19 patients.

Methods: A systematic literature search was done using relevant terms for 'COVID-19' and 'interferon-β'. Randomised controlled trials (RCT) evaluating the efficacy of interferon-β in COVID-19 were included. Data were extracted for outcome measures, namely mortality, time to clinical improvement and length of hospital stay. Random effects meta-analysis was performed using RevMan V.5.4.1 to calculate overall effect estimate as odds ratio/hazard ratio for categorical variables and mean difference for continuous variable.

Result: Eight RCTs were eligible for qualitative synthesis and seven for meta-analysis. The overall effect estimate (odds ratio [OR] 0.59; 95 % CI 0.91, 1.12) and (mean difference [MD] - 1.41; 95 % CI - 2.84, 0.02) indicated no statistically significant difference between effect of IFN-β and that of control on mortality and length of hospital stay, respectively. However, the overall effect estimate (hazard ratio [HR] 1.95; 95 % CI 1.36, 2.79) denoted a favourable effect of INF-β on reducing the time to clinical improvement in moderate-to-severe COVID-19 patients.

Conclusion: Addition of interferon-β to standard of care resulted in significant reduction in time to clinical improvement but no significant benefit in terms of reduction in mortality and length of hospital stay in moderate-to-severe cases of COVID-19.
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http://dx.doi.org/10.1007/s40261-021-01092-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540871PMC
December 2021

Characteristic imaging finding and spot radiological diagnosis in a young man with acute breathlessness and chest pain.

Adv Respir Med 2021;89(5):538-539. Epub 2021 Oct 20.

All India Institute of Medical Sciences, Gorakhpur, India.

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http://dx.doi.org/10.5603/ARM.a2021.0073DOI Listing
February 2022

Dysregulated APOBEC3G causes DNA damage and promotes genomic instability in multiple myeloma.

Blood Cancer J 2021 10 8;11(10):166. Epub 2021 Oct 8.

Dana Farber Cancer Institute, Boston, MA, 02115, USA.

Multiple myeloma (MM) is a heterogeneous disease characterized by significant genomic instability. Recently, a causal role for the AID/APOBEC deaminases in inducing somatic mutations in myeloma has been reported. We have identified APOBEC/AID as a prominent mutational signature at diagnosis with further increase at relapse in MM. In this study, we identified upregulation of several members of APOBEC3 family (A3A, A3B, A3C, and A3G) with A3G, as one of the most expressed APOBECs. We investigated the role of APOBEC3G in MM and observed that A3G expression and APOBEC deaminase activity is elevated in myeloma cell lines and patient samples. Loss-of and gain-of function studies demonstrated that APOBEC3G significantly contributes to increase in DNA damage (abasic sites and DNA breaks) in MM cells. Evaluation of the impact on genome stability, using SNP arrays and whole genome sequencing, indicated that elevated APOBEC3G contributes to ongoing acquisition of both the copy number and mutational changes in MM cells over time. Elevated APOBEC3G also contributed to increased homologous recombination activity, a mechanism that can utilize increased DNA breaks to mediate genomic rearrangements in cancer cells. These data identify APOBEC3G as a novel gene impacting genomic evolution and underlying mechanisms in MM.
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http://dx.doi.org/10.1038/s41408-021-00554-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501035PMC
October 2021
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