Publications by authors named "Sathish Kumar"

275 Publications

1,2-Phenylene-Incorporated Smallest Expanded Calix[4]pyrrole via One-Step Synthesis of Tetrapyrrane: A Fluorescent Host for Fluoride Ion.

J Org Chem 2021 Jul 28. Epub 2021 Jul 28.

School of Chemistry, University of Hyderabad, Hyderabad 500046, India.

Synthesis of tetrapyrrane from acetone and pyrrole via one-step condensation was achieved for the first time along with a much-improved yield of the tripyrrane . Diborylation of the tetrapyrrane and subsequent "1 + 1" cyclocoupling with 1,2-diiodobenzene following the Suzuki protocol generated novel -phenylene incorporated macrocycle belonging to the smallest -expanded calix[4]pyrrole family. The latter macrocycle displays exclusive fluorescence sensing of fluoride ion upon complexation via a unique partial cone conformation supported by DFT analysis in acetonitrile solvent.
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http://dx.doi.org/10.1021/acs.joc.1c01179DOI Listing
July 2021

A systematic review on the effect of low-dose radiation on hearing.

Radiat Environ Biophys 2021 Jul 24. Epub 2021 Jul 24.

Department of Pharmacology, Kasturba Medical College, Manipal Academy of Higher Education, Mangalore, 575001, India.

Numerous studies have documented the adverse effects of high-dose radiation on hearing in patients. On the other hand, radiographers are exposed to a low dose of ionizing radiation, and the effect of a low dose of radiation on hearing is quite abstruse. Therefore, the present systematic review aimed to elucidate the effect of low-dose ionizing radiation on hearing. Two authors independently carried out a comprehensive data search in three electronic databases, including PUBMED/MEDLINE, CINAHL, and SCOPUS. Eligible articles were independently assessed for quality by two authors. Cochrane Risk of Bias tool was used assess quality of the included studies. Two articles met the low-dose radiation exposure criteria given by Atomic Energy Regulatory Board (AERB) and National Council on Radiation Protection (NCRP) guidelines. Both studies observed the behavioral symptoms, pure-tone hearing sensitivity at the standard, extended high frequencies, and the middle ear functioning in low-dose radiation-exposed individuals and compared with age and gender-matched controls. One study assessed the cochlear function using transient-evoked otoacoustic emissions (TEOAE). Both studies reported that behavioral symptoms of auditory dysfunction and hearing thresholds at extended high frequencies were higher in radiation-exposed individuals than in the controls. The current systematic review concludes that the low-dose ionizing radiation may affect the hearing adversely. Nevertheless, further studies with robust research design are required to explicate the cause and effect relationship between the occupational low-dose ionizing radiation exposure and hearing.
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http://dx.doi.org/10.1007/s00411-021-00926-6DOI Listing
July 2021

Formation of nanostructures on magnesium alloy by anodization for potential biomedical applications.

Mater Today Commun 2020 Dec 29;25. Epub 2020 Jun 29.

Department of Engineering Design, Indian Institute of Technology Madras, India.

In the present work, we have investigated the formation of nanostructures on AZ31 magnesium alloy using electrochemical anodization technique. The formed nanostructures were efficiently showed bone-like apatite formation followed by its gradual increase, when immersed in simulated body fluid (SBF) and it exhibited controlled degradation in 7 days. Cell viability study was performed using MG-63 cells (human osteosarcoma cell lines) and revealed that the nanostructured surface has excellent biocompatibility by enhancing both cell adhesion and cell growth. The detailed characterization of this anodized surface was evaluated by field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDS). Furthermore, surface-corrosion before and after anodization was examined by electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization studies in SBF. The in-depth studies bring out the fact that native oxide in the sample is converted to a biocompatible nanostructure, which is created due to anodization in a particular electrolyte solution containing ethylene glycol and hybrid hydrofluoric acid mixture.
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http://dx.doi.org/10.1016/j.mtcomm.2020.101403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611340PMC
December 2020

AB- and A-Type Boron(III)Subchlorins Derived from -Diethoxycarbonyltripyrrane: Synthesis and Photophysical Exploration.

J Org Chem 2021 Jul 15. Epub 2021 Jul 15.

School of Chemistry, University of Hyderabad, Hyderabad 500046, India.

The first direct fabrication of AB- and A-type B(III)subchlorins from ethoxycarbonyl-substituted tripyrrane has been realized by condensation with appropriate acid chlorides (benzoyl chloride, butyryl chloride, and ethyl chlorooxoacetate). The aliphatic acid chloride-based annulation reaction is new to subporphyrinoid chemistry. The phenyl ()- or -propyl ()-substituted derivatives could be oxidized to the corresponding B(III)subporphyrins upon refluxing with DDQ, whereas the triethoxycarbonyl moiety () was found to be resistant to oxidation and exhibits the most red-shifted absorption (587 nm) and emission (604 nm). The study indicates that absorption and emission behaviors of the B(III)subchlorin can be tuned by the introduction of electron-rich or electron-deficient substituents at the -position. B(III)subchlorins and generate singlet oxygen efficiently (44 and 40%, respectively) and, thus, may find application as potential photosensitizers in photodynamic therapy (PDT).
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http://dx.doi.org/10.1021/acs.joc.1c01001DOI Listing
July 2021

Clinical Spectrum of Children With Multisystem Inflammatory Syndrome Associated With SARS-CoV-2 Infection.

Indian Pediatr 2021 Jun 28. Epub 2021 Jun 28.

Pediatric Intensive care unit, Department of Pediatrics, Christian Medical College, Vellore, Tamil Nadu.

Objective: To compare the clinical profile, treatment, and outcomes of PCR-positive and PCR-negative antibody-positive critically ill children with multisystem inflammatory syndrome (MIS-C).

Methods: This retrospective observational study was done at a tertiary care coronavirus disease 19 (COVID-19) pediatric intensive care unit in India. The baseline characteristics, clinical profile, treatment, and outcomes in seventeen critically ill children diagnosed with MIS-C were analyzed from 1 July to 31 October, 2020.

Results: Sixteen out of 17 children presented with hypotensive shock and respiratory distress. Mean (SD) age of PCR-negative antibody-positive and PCR-positive children was 11 (4.4) and 5 (3.7) years, respectively; P=0.007. The former group had significantly higher mean (SD) D-dimer levels [16,651 (14859) ng/mL vs 3082 (2591) ng/mL; P=0.02]. All received intensive care management and steroid therapy; 7 children received intravenous immunoglobulin. 14 children survived and 3 died.

Conclusion: The outcome of children with MIS-C was good if recognized early and received intensive care.
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June 2021

Contributions of the international plant science community to the fight against infectious diseases in humans-part 2: Affordable drugs in edible plants for endemic and re-emerging diseases.

Plant Biotechnol J 2021 Jun 28. Epub 2021 Jun 28.

Department of Chemical Engineering, University of California, Davis, Davis, CA, USA.

The fight against infectious diseases often focuses on epidemics and pandemics, which demand urgent resources and command attention from the health authorities and media. However, the vast majority of deaths caused by infectious diseases occur in endemic zones, particularly in developing countries, placing a disproportionate burden on underfunded health systems and often requiring international interventions. The provision of vaccines and other biologics is hampered not only by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, but also by challenges caused by distribution and storage, particularly in regions without a complete cold chain. In this review article, we consider the potential of molecular farming to address the challenges of endemic and re-emerging diseases, focusing on edible plants for the development of oral drugs. Key recent developments in this field include successful clinical trials based on orally delivered dried leaves of Artemisia annua against malarial parasite strains resistant to artemisinin combination therapy, the ability to produce clinical-grade protein drugs in leaves to treat infectious diseases and the long-term storage of protein drugs in dried leaves at ambient temperatures. Recent FDA approval of the first orally delivered protein drug encapsulated in plant cells to treat peanut allergy has opened the door for the development of affordable oral drugs that can be manufactured and distributed in remote areas without cold storage infrastructure and that eliminate the need for expensive purification steps and sterile delivery by injection.
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http://dx.doi.org/10.1111/pbi.13658DOI Listing
June 2021

Discovery of pan-ErbB inhibitors protecting from SARS-CoV-2 replication, inflammation, and lung injury by a drug repurposing screen.

bioRxiv 2021 Jun 15. Epub 2021 Jun 15.

Effective therapies are needed to combat emerging viruses. Seventeen candidates that rescue cells from SARS-CoV-2-induced lethality and target diverse functions emerged in a screen of 4,413 compounds. Among the hits was lapatinib, an approved inhibitor of the ErbB family of receptor tyrosine kinases. Lapatinib and other pan-ErbB inhibitors suppress replication of SARS-CoV-2 and unrelated viruses with a high barrier to resistance. ErbB4, but not lapatinib's cancer targets ErbB1 and ErbB2, is required for SARS-CoV-2 entry and encephalitis alphavirus infection and is a molecular target mediating lapatinib's antiviral effect. In human lung organoids, lapatinib protects from SARS-CoV-2-induced activation of pathways implicated in non-infectious acute lung injury and fibrosis downstream of ErbBs (p38-MAPK, MEK/ERK, and AKT/mTOR), pro-inflammatory cytokine production, and epithelial barrier injury. These findings reveal regulation of viral infection, inflammation, and lung injury via ErbBs and propose approved candidates to counteract these effects with implications for pandemic coronaviruses and unrelated viruses.
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http://dx.doi.org/10.1101/2021.05.15.444128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219101PMC
June 2021

Closed-tube field-deployable loop-mediated isothermal amplification (LAMP) assay based on spore wall protein (SWP) for the visual detection of Enterocytozoon hepatopenaei (EHP).

J Invertebr Pathol 2021 Jul 30;183:107624. Epub 2021 May 30.

ICAR-Central Institute of Brackishwater Aquaculture, #75 Santhome High Road, MRC Nagar, Chennai, India.

Hepatopancreatic microsporidiosis (HPM) is an infectious shrimp disease caused by the microsporidian Enterocytozoon hepatopenaei (EHP). In recent years, the widespread occurrence of EHP poses a significant challenge to the shrimp aquaculture industry. Early, rapid and accurate diagnosis of EHP infection is very much essential for the control of HPM crop-related losses. Loop-mediated isothermal amplification (LAMP) is a robust, sensitive, cost-effective disease diagnostic technique. Here, we demonstrate an improved, simple, closed-tube, colorimetric EHP LAMP diagnostic assay. LAMP assay was illustrated with the specific EHP spore wall protein (SWP) gene primers. Naked eye visual detection of LAMP amplicons was achieved using Hydroxy naphthol blue (HNB) or Phenol red dye without opening the tubes. This LAMP assay is efficient in detecting the EHP pathogen in all clinical samples include shrimp hepatopancreas, FTA card samples, feces, pond water, and soil. Also, the elution of EHP DNA from FTA cards was demonstrated within 17 min using a simple dry bath. In clinical evaluation, the visual LAMP assay established 100% diagnostic sensitivity and 100% diagnostic specificity. The visual LAMP assay is rapid, can detect the EHP pathogen within 40 min using a simple dry bath, and does not require any expensive instruments and technical proficiency. In conclusion, this visual LAMP protocol is a user-friendly, specific assay that can be conceivably operated at the farm-site/ resource-limited settings by the farmer himself with simple equipment.
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http://dx.doi.org/10.1016/j.jip.2021.107624DOI Listing
July 2021

In-vivo dose measurements with MOSFET dosimeters during MV portal imaging.

Rep Pract Oncol Radiother 2021 25;26(1):93-100. Epub 2021 Feb 25.

Department of Radiation Oncology, Christian Medical College, Vellore, India.

Background: The purpose of this study was to investigate the feasibility of MOSFET dosimeter in measuring eye dose during 2D MV portal imaging for setup verification in radiotherapy.

Materials And Methods: The in-vivo dose measurements were performed by placing the dosimeters over the eyes of 30 brain patients during the acquisition of portal images in linear accelerator by delivering 1 MU with the field sizes of 10 × 10 cm and 15 × 15 cm.

Results: The mean doses received by the left and right eyes of 10 out of 30 patients when both eyes were completely inside the anterior portal field were found to be 2.56 ± 0.2 cGy and 2.75 ± 0.2, respectively. Similarly, for next 10 patients out of the same 30 patients the mean doses to left and right eyes when both eyes were completely out of the anterior portal fields were found to be 0.13 ± 0.02 cGy and 0.17 ± 0.02 cGy, respectively. The mean doses to ipsilateral and contralateral eye for the last 10 patients when one eye was inside the anterior portal field were found to be 3.28 ± 0.2 cGy and 0.36 ± 0.1 cGy, respectively.

Conclusion: The promising results obtained during 2D MV portal imaging using MOSFET have shown that this dosimeter is well suitable for assessing low doses during imaging thereby enabling to optimize the imaging procedure using the dosimetric data obtained. In addition, the documentation of the dose received by the patient during imaging procedure is possible with the help of an in-built software in conjunction with the MOSFET reader module.
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http://dx.doi.org/10.5603/RPOR.a2021.0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149133PMC
February 2021

A prospective cohort study of patients presenting to the emergency department with upper gastrointestinal bleeding.

J Family Med Prim Care 2021 Mar 8;10(3):1431-1436. Epub 2021 Apr 8.

Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India.

Background: Upper gastrointestinal (UGI) bleeding is a common presentation to the Emergency Department (ED), and is associated with re-bleeding and significant mortality. Although several studies have described etiology and outcome of UGI bleeding, few have been done in the EDs.

Materials And Methods: This prospective observational cohort study included all patients presenting with hematemesis or melena, between June 2016 and January 2017 to the ED. Demographic data, risk factors, endoscopy findings and prognosticating scores were noted. Patients were followed up through telephonic communication after 3 months to assess re-bleeding rate and mortality.

Results: The study cohort included 210 patients with a male predominance (76.2%). The mean (SD) age was 51 (16.8) years. They presented with either hematemesis (33.8%), melena (28.6%), or both (37.6%). One third (35.7%) had variceal bleed, 21% had peptic ulcer disease (PUD), and 43.3%bled due to other etiology. UGI scopy was performed in 85.2% of patients with banding (25.1%) and sclerotherapy (14%) being the most frequently performed procedures. Endoscopic intervention was not required in 58.6%of patients. Packed red cells were transfused in 46.7% patients. The 48-h re-bleed rate among variceal bleeders was 5.3% and 11.4% among peptic ulcer bleeders. The 3-month re-bleeding rate was 42.9% and the 3-month mortality rate was 17.5% among the variceal bleeders and the same was 5.6% and 2.8%, respectively, among the peptic ulcer bleeders. The overall mortality was 12.4%.

Conclusions: Variceal bleeding and PUD were the predominant causes of UGI bleeding. Overall, a quarter of our patients had a re-bleed within 3 months, with majority being variceal bleeds.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1996_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140221PMC
March 2021

Behavioral Biometric Data Analysis for Gender Classification Using Feature Fusion and Machine Learning.

Front Robot AI 2021 7;8:685966. Epub 2021 May 7.

Department of MCA, KLE Technological University, Hubballi, India.

Biometric security applications have been employed for providing a higher security in several access control systems during the past few years. The handwritten signature is the most widely accepted behavioral biometric trait for authenticating the documents like letters, contracts, wills, MOU's, etc. for validation in day to day life. In this paper, a novel algorithm to detect gender of individuals based on the image of their handwritten signatures is proposed. The proposed work is based on the fusion of textural and statistical features extracted from the signature images. The LBP and HOG features represent the texture. The writer's gender classification is carried out using machine learning techniques. The proposed technique is evaluated on own dataset of 4,790 signatures and realized an encouraging accuracy of 96.17, 98.72 and 100% for k-NN, decision tree and Support Vector Machine classifiers, respectively. The proposed method is expected to be useful in design of efficient computer vision tools for authentication and forensic investigation of documents with handwritten signatures.
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http://dx.doi.org/10.3389/frobt.2021.685966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139629PMC
May 2021

Efficacy of paravertebral block in "Fast-tracking" pediatric cardiac surgery - Experiences from a tertiary care center.

Ann Card Anaesth 2021 Jan-Mar;24(1):24-29

Department of Cardiothoracic Surgery, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.

Introduction: Fast tracking plays a crucial role in reducing perioperative morbidity and financial burden by facilitating early extubation and discharge from hospital. Paravertebral block (PVB) is becoming more popular in paediatric surgeries as an alternative to epidural and caudal analgesia. There is scarcity of data regarding the efficacy and safety of PVB in paediatric cardiac surgery.

Methods: We performed a review of records of paediatric cardiac patients who underwent cardiac surgery under general anaesthesia with single shot PVB and compared the analgesia and postoperative outcomes with matched historical controls who underwent cardiac surgery with same anaesthesia protocol without PVB.

Results: The data from 200 children were analysed. 100 children who received paravertebral block were compared with a matched historical controls. The median time to extubation was shorter in the PVB group (0 hr, IQR 0-3 hrs) compared to the control group (16 hrs, IQR 4-20 hrs) (P value 0.017*). Intraoperative and postoperative fentanyl requirement was much lower in the PVB group (3.49 (0.91)) compared to the control group (9.86 (1.37)) P value <0.01*. Time to first rescue dose of analgesic was longer (7 hrs vs 5 hrs, P 0.01*), while time to extubation and duration of ICU stay were significantly less in PVB group . Mean postoperative pain scores were significantly lower in the PVB group at the time of ICU admission (0.85 vs 3.12, P 0.001*) till 4 hours (2.11 vs 3.32, P 0.001*).

Conclusion: PVB provides an effective and safe anaesthetic approach which can form an important component of "fast-track" care in paediatric cardiac surgery.
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http://dx.doi.org/10.4103/aca.ACA_83_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081147PMC
May 2021

Evaluation of beeswax coated coconut shells for packaging of set-type : an Indian fermented product.

J Food Sci Technol 2021 May 16;58(5):2019-2027. Epub 2020 Aug 16.

Food Packaging Technology Department, CFTRI, Mysore, India.

An attempt was made to develop coconut shell-based eco-friendly packaging material for the packaging of set-type . Beeswax was used to improve the moisture barrier properties of coconut shell (CS). UV treatment for 60 min showed complete disinfection of the coconut shell surface. The top open side of the coconut shell was sealed with aluminium foil using pectin solution as adhesive. Set-type was prepared and packaged in beeswax coated CS (BCCS) and evaluated for physico-chemical, textural, sensorial and microbiological quality changes for a period of 21 days at 6 ± 1 °C. The rate of increase in acidity was found slower in BCCS as compared to packaged in polypropylene cups (control). There was no whey separation, consequently water-holding capacity and firmness of product were better in packaged in BCCS. The sensorial analysis revealed better body and texture properties for packaged in BCCS. However, the flavour score of packaged in BCCS decreased comparatively after 12 days due to the absorption of coconut flavor by the product. These findings demonstrated the potential of coconut shell based eco-friendly packaging material for packaging set-type and thereby aim to reduce the use of non-biodegradable plastics.
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http://dx.doi.org/10.1007/s13197-020-04714-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021658PMC
May 2021

Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study.

Public Health Genomics 2021 Apr 6:1-10. Epub 2021 Apr 6.

Department of Child Health, Christian Medical College, Vellore, India.

Introduction: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder, in which biallelic pathogenic variants in the Glucosidase beta acid (GBA) gene result in defective functioning of glucosylceramidase that causes deposition of glucocerebroside in cells. GD has 3 major types namely, non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). Definite treatment options are limited and expensive. They succumb early to the disease, if untreated. There is paucity of studies from the Indian subcontinent, which elicit the factors resulting in their premature mortality.

Materials And Methods: A retrospective study was carried out in a tertiary care setting of South India to assess the clinical profile, mutation spectrum, and various management strategies (only supportive therapy, enzyme replacement therapy [ERT], substrate reduction therapy [SRT] haematopoietic stem cell transplant [HSCT]), and mortality predictors of patients with GD from 2004 to 2019. A Kaplan-Meier survival curve was plotted. In silico predictions were performed for novel variants.

Results: There were 60 patients with all types of GD seen over the study period of 15 years. Their median age at diagnosis was 2 years. The median follow-up was for 5 years (interquartile range [IQR] = 2-8). The overall mortality rate was 35%; however, it was only 10% in those receiving definite treatment. Mortality was higher (47.5%) by more than 4 folds in those only on supportive therapy. The median survival from the time of diagnosis was 6.3 years (IQR = 3.5-10.8) in the definite treatment group and 3.5 years (IQR = 1-5) in those on supportive therapy. The Kaplan-Meier survival analysis showed significant (p value 0.001) mortality difference between these groups. The multiple logistic regression analysis found the neuronopathic type (OR = 5) and only supportive therapy (OR = 6.3) to be the independent risk factors for premature mortality.

Conclusion: GD is a rare disease with a high mortality rate, if left untreated. ERT and SRT are the definitive treatments which increase the survival. In resource-limited settings like India, with higher prevalence of the neuronopathic type, HSCT may be a more suitable definitive treatment option, due to its one-time intervention and cost, assuming similar efficacy to ERT. However, the efficacy and safety of HSCT in GD needs to be established further by substantial patient numbers undergoing it.
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http://dx.doi.org/10.1159/000514507DOI Listing
April 2021

The transcriptional landscape of Venezuelan equine encephalitis virus (TC-83) infection.

PLoS Negl Trop Dis 2021 03 31;15(3):e0009306. Epub 2021 Mar 31.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.

Venezuelan Equine Encephalitis Virus (VEEV) is a major biothreat agent that naturally causes outbreaks in humans and horses particularly in tropical areas of the western hemisphere, for which no antiviral therapy is currently available. The host response to VEEV and the cellular factors this alphavirus hijacks to support its effective replication or evade cellular immune responses are largely uncharacterized. We have previously demonstrated tremendous cell-to-cell heterogeneity in viral RNA (vRNA) and cellular transcript levels during flaviviral infection using a novel virus-inclusive single-cell RNA-Seq approach. Here, we used this unbiased, genome-wide approach to simultaneously profile the host transcriptome and vRNA in thousands of single cells during infection of human astrocytes with the live-attenuated vaccine strain of VEEV (TC-83). Host transcription was profoundly suppressed, yet "superproducer cells" with extremely high vRNA abundance emerged during the first viral life cycle and demonstrated an altered transcriptome relative to both uninfected cells and cells with high vRNA abundance harvested at later time points. Additionally, cells with increased structural-to-nonstructural transcript ratio exhibited upregulation of intracellular membrane trafficking genes at later time points. Loss- and gain-of-function experiments confirmed pro- and antiviral activities in both vaccine and virulent VEEV infections among the products of transcripts that positively or negatively correlated with vRNA abundance, respectively. Lastly, comparison with single cell transcriptomic data from other viruses highlighted common and unique pathways perturbed by infection across evolutionary scales. This study provides a high-resolution characterization of the VEEV (TC-83)-host interplay, identifies candidate targets for antivirals, and establishes a comparative single-cell approach to study the evolution of virus-host interactions.
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http://dx.doi.org/10.1371/journal.pntd.0009306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041203PMC
March 2021

Activation of angiotensin type 2 receptor attenuates testosterone-induced hypertension and uterine vascular resistance in pregnant rats†.

Biol Reprod 2021 Jul;105(1):192-203

Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.

Preeclampsia is a pregnancy-related hypertensive disorder with unclear mechanisms. While hypersensitivity to angiotensin II via vasoconstrictive angiotensin type-1 receptor (AT1R) is observed in preeclampsia, the importance of vasodilatory angiotensin type-2 receptor (AT2R) in the control of vascular dysfunction is less clear. We assessed whether AT1R, AT2R, and endothelial nitric oxide synthase (eNOS) expression are altered in placental vessels of preeclamptic women and tested if ex vivo incubation with AT2R agonist Compound 21 (C21; 1 μM) could restore AT1R, AT2R, and eNOS balance. Further, using a rat model of gestational hypertension induced by elevated testosterone, we examined whether C21 (1 μg/kg/day, oral) could preserve AT1R and AT2R balance and improve blood pressure, uterine artery blood flow, and vascular function. Western blots revealed that AT1R protein level was higher while AT2R and eNOS protein were reduced in preeclamptic placental vessels, and AT2R agonist C21 decreased AT1R and increased AT2R and eNOS protein levels in preeclamptic vessels. In testosterone dams, blood pressure was higher, and uterine artery blood flow was reduced, and C21 treatment reversed these levels similar to those in controls dams. C21 attenuated the exaggerated Ang II contraction and improved endothelium-dependent vasorelaxation in uterine arteries of testosterone dams. These C21-mediated vascular effects were associated with decreased AT1R and increased AT2R and eNOS protein levels. C21 also increased serum nitrate/nitrite and bradykinin production in testosterone dams and attenuated the fetoplacental growth restriction. Thus, AT1R upregulation and AT2R downregulation are observed in preeclampsia and testosterone model, and increasing AT2R activity could help restore AT1R and AT2R balance and improve gestational vascular function.
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http://dx.doi.org/10.1093/biolre/ioab051DOI Listing
July 2021

Recurrent mucormycosis - Better understanding of treatment and management.

J Family Med Prim Care 2020 Dec 31;9(12):6279-6281. Epub 2020 Dec 31.

Department of Oral and Maxillofacial Surgery, Karpaga Vinayaga Institute of Dental Sciences, Chinna Kolambakkam, Kanchipuram Dist., Madurantagam, Tamil Nadu, India.

Mucormycosis is a rare opportunistic, aggressive, fatal fungal infection. The fungal organisms are ubiquitous and easily affect immunocompromised patients. It is spread on inhalation, inoculation and wound contamination and is more common in diabetic and other immunocompromised individuals in a population. The clinical and radiological features of Mucormycosis can overlap with other conditions for which a thorough diagnosis should be made. The rate of recurrence in Mucormycosis cases is high. This article reports one such case in which recurrence occurred twice and was controlled only with resection. The main aim of this article is to emphasize the importance of practicing aggressive resection and also on regular follow up of the patient after surgical management. Knowledge on different diagnostic and treatment methods, availability of newer drugs and regular follow up can greatly help in the management and recurrence of Mucormycosis even in immunocompromised patients in a population where diabetes is more common and mortality of rhino cerebral form is high.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1220_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928079PMC
December 2020

Polyradiculopathy and Multiple Cranial Nerve Palsies - Rare Manifestations of Cerebral Venous Sinus Thrombosis.

Neurol India 2021 Jan-Feb;69(1):170-173

Department of Neurology, Stanley Medical College, Chennai, Tamil Nadu, India.

We report about two young males who developed significant proximal weakness of all four limbs secondary to intracranial hypertension due to intracranial venous sinus thrombosis. Intracranial venous sinus thrombosis can manifest in a variety of ways which includes isolated intracranial hypertension, focal neurological symptoms or signs and acute or subacute encephalopathy. Various false localising signs have been reported to occur in patients with raised intracranial pressure including cranial nerve palsies and extensive radiculopathy. In a patient presenting with flaccid areflexic quadriparesis and papilledema, the possibility of a potentially reversible dysfunction of the cranial nerves and spinal nerve roots due to a marked rise in intracranial and intraspinal pressure must be recognised. Lumboperitoneal shunt to reduce the intraspinal pressure on the spinal nerve roots has been advocated to reverse the symptoms of extensive radiculopathy in such patients. Both of our patients showed remarkable improvement in symptoms and signs with medical treatment of CVT.
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http://dx.doi.org/10.4103/0028-3886.310084DOI Listing
June 2021

Novel Phosphorylation-State Specific Antibodies Reveal Differential Deposition of Ser26 Phosphorylated Aβ Species in a Mouse Model of Alzheimer's Disease.

Front Mol Neurosci 2020 15;13:619639. Epub 2021 Jan 15.

Department of Neurology, University of Bonn Medical Center, Bonn, Germany.

Aggregation and deposition of amyloid-β (Aβ) peptides in extracellular plaques and in the cerebral vasculature are prominent neuropathological features of Alzheimer's disease (AD) and closely associated with the pathogenesis of AD. Amyloid plaques in the brains of most AD patients and transgenic mouse models exhibit heterogeneity in the composition of Aβ deposits, due to the occurrence of elongated, truncated, and post-translationally modified Aβ peptides. Importantly, changes in the deposition of these different Aβ variants are associated with the clinical disease progression and considered to mark sequential phases of plaque and cerebral amyloid angiopathy (CAA) maturation at distinct stages of AD. We recently showed that Aβ phosphorylated at serine residue 26 (pSer26Aβ) has peculiar characteristics in aggregation, deposition, and neurotoxicity. In the current study, we developed and thoroughly validated novel monoclonal and polyclonal antibodies that recognize Aβ depending on the phosphorylation-state of Ser26. Our results demonstrate that selected phosphorylation state-specific antibodies were able to recognize Ser26 phosphorylated and non-phosphorylated Aβ with high specificity in enzyme-linked immunosorbent assay (ELISA) and Western Blotting (WB) assays. Furthermore, immunofluorescence analyses with these antibodies demonstrated the occurrence of pSer26Aβ in transgenic mouse brains that show differential deposition as compared to non-phosphorylated Aβ (npAβ) or other modified Aβ species. Notably, pSer26Aβ species were faintly detected in extracellular Aβ plaques but most prominently found intraneuronally and in cerebral blood vessels. In conclusion, we developed new antibodies to specifically differentiate Aβ peptides depending on the phosphorylation state of Ser26, which are applicable in ELISA, WB, and immunofluorescence staining of mouse brain tissues. These site- and phosphorylation state-specific Aβ antibodies represent novel tools to examine phosphorylated Aβ species to further understand and dissect the complexity in the age-related and spatio-temporal deposition of different Aβ variants in transgenic mouse models and human AD brains.
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http://dx.doi.org/10.3389/fnmol.2020.619639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844098PMC
January 2021

Assessment of ecological health of Swarnamukhi river estuary, southeast coast of India, through AMBI indices and multivariate tools.

Mar Pollut Bull 2021 Mar 27;164:112031. Epub 2021 Jan 27.

National Institute of Ocean Technology (Ministry of Earth Sciences, Govt. of India), Chennai 600100, India. Electronic address:

A combination of biotic indices, geo-accumulation (I) index, and a multivariate approach were applied to assess the anthropogenic influence on the benthic community at five stations from 2018 to 2019 in the Swarnamukhi river estuary, Nellore, India. Non-metric multidimensional scaling and cluster analysis indicated that the Buckingham canal (BC) station showed azoic conditions and formed a separate cluster. Strong positive factor loadings of Cd (0.96), Al (0.93), Zn (0.91), Fe (0.90), Co (0.89), Cu (0.89), Ni (0.87), Pb (0.85), Cr (0.77), organic matter (0.94), Silt (0.92), and clay (0.93) and negative loading of sand (-0.90) showed the variability in sediment. AMBI results illustrated the disturbance status of each station and classified BC station as 'extremely disturbed' class, and M-AMBI assessed the ecological status as 'bad'. The I index also revealed metal (Cd) contamination. The present study illustrated that the combined approach is effective for ecological assessment of coastal ecosystem.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112031DOI Listing
March 2021

Multifunctional Sutures with Temperature Sensing and Infection Control.

Macromol Biosci 2021 03 12;21(3):e2000364. Epub 2021 Jan 12.

College of Science, Engineering and Health, School of Engineering, RMIT University, Melbourne, 3001, Australia.

The next-generation sutures should provide in situ monitoring of wound condition such as temperature while reducing surgical site infection during wound closure. In this study, functionalized nanodiamond (FND) and reduced graphene oxide (rGO) into biodegradable polycaprolactone (PCL) are incorporated to develop a new multifunctional suture with such capabilities. Incorporation of FND and rGO into PCL enhances its tensile strength by about 43% and toughness by 35%. The sutures show temperature sensing capability in the range of 25-40 °C based on the shift in zero-splitting frequency of the nitrogen-vacancy (NV ) centers in FND via optically detected magnetic resonance, paving the way for potential detection of infection or excessive inflammation in healing wounds. The suture surface readily coats with antibiotics to reduce bacterial infection risk to the wounds. The new suture thus is promising in monitoring and supporting wound closure.
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http://dx.doi.org/10.1002/mabi.202000364DOI Listing
March 2021

ZnCl catalyzed new coumarinyl-chalcones as cytotoxic agents.

Saudi J Biol Sci 2021 Jan 22;28(1):386-394. Epub 2020 Oct 22.

Department of Chemistry, College of Science, King Khalid University, Abha, Saudi Arabia.

A new series of coumarin-yl-chalcone derivatives () had been designed and synthesized through different reactions such as aromatic addition, cyclization and Claisen-Schmidt reactions in good yields (54-78%). 5-acetyl-4-(2-hydroxyphenyl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one has been synthesized by multi-component one pot reaction of salicylaldehyde, methyl acetoacetate and urea, which was further reacted with malonic acid employing ZnCl catalyst to yield 5-acetyl-4-(4-hydroxy-2-oxo-2-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1) -one The title compounds ( were synthesised by reacting 5-acetyl-4-(4-hydroxy-2-oxo-2-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1)-one () with different aromatic aldehydes in the presence of potassium hydroxide. studies, a preliminary screening method for predicting the anti-cancer activity was performed for the synthesized compounds ( against Src, Alb tyrosine kinase and homology model protein (PDB ID: 4csv). The derivatives and showed moderate binding energies. The cytotoxic activity was evaluated for the compounds and by using human cancer cell-line morphology and MTT assay against three human cell-lines A549 (Lung), Jurkat (Leukemia) and MCF-7 (Breast). The results indicate that the derivatives and display significant anti-cancer activity, however it was found to be less cytotoxic when compared to the standard used i.e. Imatinib.
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http://dx.doi.org/10.1016/j.sjbs.2020.10.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783654PMC
January 2021

Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease.

iScience 2021 Jan 11;24(1):101924. Epub 2020 Dec 11.

Centre for Neuroscience, Indian Institute of Science, Bangalore 560012, India.

Despite intuitive insights into differential proteolysis of amyloid precursor protein (APP), the stochasticity behind local product formation through amyloidogenic pathway at individual synapses remain unclear. Here, we show that the major components of amyloidogenic machinery namely, APP and secretases are discretely organized into nanodomains of high local concentration compared to their immediate environment in functional zones of the synapse. Additionally, with the aid of multiple models of Alzheimer's disease (AD), we confirm that this discrete nanoscale chemical map of amyloidogenic machinery is altered at excitatory synapses. Furthermore, we provide realistic models of amyloidogenic processing in unitary vesicles originating from the endocytic zone of excitatory synapses. Thus, we show how an alteration in the stochasticity of synaptic nanoscale organization contributes to the dynamic range of C-terminal fragments β (CTFβ) production, defining the heterogeneity of amyloidogenic processing at individual synapses, leading to long-term synaptic deficits as seen in AD.
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http://dx.doi.org/10.1016/j.isci.2020.101924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773964PMC
January 2021

Formation and weathering assessment of oil-suspended sediment aggregates through a laboratory investigation.

Environ Sci Pollut Res Int 2021 Apr 4;28(14):17181-17199. Epub 2021 Jan 4.

Environmental Science Center, Qatar University, P.O Box: 2713, Doha, Qatar.

Formation of oil-suspended sediment aggregates (OSAs) is believed to be one of the natural cleaning processes in the marine environment. In this study, we have investigated the formation processes of OSAs under different mixing periods (continuous mixing and with the addition of sediments in between), oil-sediment ratios (1:1, 1:2 and 2:1) and crude oils (Arabian Light (AL), Kuwait (KW) and Murban (MB)). The results revealed that size of OSAs significantly increased (up to ≈ 1.41 mm) with the addition of sediments. Aggregates (total 36) were extracted for n-alkanes and polycyclic aromatic hydrocarbons to quantify and assess their weathering and toxic levels. The maximum n-alkane depletion was 84% (111-02), 94% (212-02) and 84% (321-02) and PAH depletion was ≈ 72% (111-02), 79% (212-02) and 81% (311-03) for the OSAs of AL, KW and MB crude oils, respectively, for the different samples considered, indicating that n-alkanes were depleted relatively higher than the PAHs. The highest depletion of both n-alkane and PAHs has occurred in OSAs of 10-h continuous mixing. The depletion of both n-alkane and PAHs reduced after the addition of sediments, however, escalated the growth of OSAs, resulting in bigger size OSAs. The concentration of PAHs of all 36 OSAs is greater than 5000 ng/g, indicating very high PAH pollution. Though the formation of OSAs helps in cleaning the spill sites, the carcinogenic threat to the marine ecosystem caused by these OSAs cannot be ignored.
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http://dx.doi.org/10.1007/s11356-020-11813-wDOI Listing
April 2021

A reporter cell system for the triggering receptor expressed on myeloid cells 2 reveals differential effects of disease-associated variants on receptor signaling and activation by antibodies against the stalk region.

Glia 2021 May 14;69(5):1126-1139. Epub 2020 Dec 14.

Department of Neurology, University of Bonn, Bonn, Germany.

The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor expressed on myeloid-derived cell types. The extracellular immunoglobulin-like domain of TREM2 binds anionic ligands including Apolipoprotein E and Amyloid-β. The transmembrane domain interacts with its adaptor protein DAP12/TYROBP that is responsible for propagation of downstream signaling upon ligand interaction. Several sequence variants of TREM2 have been linked to different neurodegenerative diseases including Alzheimer's disease. Here, we generated HEK 293 Flp-In cell lines stably expressing human TREM2 and DAP12 using a bicistronic construct with a T2A linker sequence allowing initial expression of both proteins in stoichiometric amounts. Cell biological and biochemical analyses revealed transport of TREM2 to the cell surface, and canonical sequential proteolytic processing and shedding of TREM2 (sTREM2). The functionality of this cell system was demonstrated by detection of phosphorylated spleen tyrosine kinase (SYK) upon stimulation of TREM2 with the anionic membrane lipid phosphatidylserine or anti-TREM2 antibodies. Using this cell model, we demonstrated impaired signaling of disease associated TREM2 variants. We also identified a monoclonal antibody against the stalk region of TREM2 with agonistic activity. Activation of TREM2-DAP12 signaling with the monoclonal antibody and the partial loss of function of disease associated variants were recapitulated in induced pluripotent stem cell derived microglia. Thus, this reporter cell model represents a suitable experimental system to investigate signaling of TREM2 variants, and for the identification of ligands and compounds that modulate TREM2-DAP12 signaling. MAIN POINTS: Disease associated variants impair the signaling activity of TREM2 by distinct mechanisms. Targeting the stalk region of TREM2 with bivalent antibodies activates TREM2 signaling.
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http://dx.doi.org/10.1002/glia.23953DOI Listing
May 2021

Antioxidant Activity of Telmisartan-Cu(II) Nanoparticles Connected 2-Pyrimidinamine and Their Evaluation of Cytotoxicity Activities.

Biomed Res Int 2020 18;2020:8872479. Epub 2020 Nov 18.

Research Department of Chemistry, Nehru Memorial College (Affiliated to Bharathidasan University), Puthanampatti, Tiruchirappalli District, 621007 Tamil Nadu, South India, India.

Copper nanoparticles (Cu-Nps) are one of the promising materials for the advancement of nanoscience and technology. In this work, we synthesized telmisartan copper nanoparticles and 2-pyrimidinamines via Biginelli reaction using telmisartan copper nanoparticles (Cu-Nps) as a reusable catalyst. The synthesis of 2-pyrimidinamine derivatives (1a-c) was achieved in water and under solvent-free condition (Green chemistry approach). Synthesis of 2-pyrimidinamine with telmisartan copper nanoparticle (Cu-Nps-Pyr) unexpected product was also isolated from synthesis of 2-pyrimidinamine preparation. Antioxidant and cytotoxic activities were carried out both in 2-pyrimidinamine (1a-1c) and 2-pyrimidinamine with telmisartan copper nanoparticles (Cu-Nps-Pyr). The synthesized 2-pyrimidinamine derivatives (1a-c) were characterized from FT-IR, H and C NMR spectroscopy, mass and elemental analyses. The synthesized telmisartan copper nanoparticles (Cu-Nps) were characterized from UV spectroscopy, XRD, SEM, EDX, AFM (atomic force microscopy), profile, waviness, and roughness analyses. Antioxidant activity was screened based on ABTS radical scavenging and linoleic acid peroxidation performance. Cu-Nps-Pyr-1b showed substantial antioxidant (97.2%) activity against ABTS assay and 91.2% activity against AAPH assays compared with Trolox. Cytotoxicity was evaluated using HepG2, HeLa, and MCF-7 cell lines, the Cu-Nps-Pyr-1a is high in toxicities (GI = 0.01 m) against the HeLa cancel cell line compared with doxorubicin. The developed copper NPs with 2-pyrimidinamine (Cu-Nps-Pyr) could provide promising advances as antioxidant activities; this nanocomposition could be considered an anticancer treatment in future investigations.
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http://dx.doi.org/10.1155/2020/8872479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688356PMC
May 2021

-Free Boron(III)subchlorin and Its μ-Oxo Dimer with Interacting Chromophores.

Org Lett 2020 Dec 3;22(24):9735-9739. Epub 2020 Dec 3.

School of Chemistry, University of Hyderabad, Hyderabad 500046, India.

-free B(III)subchlorin has been realized exclusively for the first time from ethoxycarbonyl-substituted tripyrrane along with the first subchlorin dimer as its μ-oxo analogue via a facile one-pot approach. The subchlorin is highly stable toward oxidation; hence, it was not contaminated with the corresponding subporphyrin analogue . The subchlorin (56%) and its dimer (30%) exhibit singlet oxygen generation ability for the first time. The B-O-B dimer displays strong exciton coupling between the two macrocycles.
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http://dx.doi.org/10.1021/acs.orglett.0c03813DOI Listing
December 2020

Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management.

Rheumatol Int 2021 01 21;41(1):19-32. Epub 2020 Nov 21.

Allergy Immunology Unit, Department of Pediatrics and Chief, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease.
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http://dx.doi.org/10.1007/s00296-020-04749-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680080PMC
January 2021

Clinical course of 602 patients with Takayasu's arteritis: comparison between Childhood-onset versus adult onset disease.

Rheumatology (Oxford) 2021 05;60(5):2246-2255

Systemic Autoimmunity Branch/NIAMS, National Institutes of Health, Bethesda, MD, USA.

Objectives: To describe the clinical profile of Asian Indian patients with Takayasu's arteritis (TAK) and to compare clinical features and outcome of childhood-onset Takayasu's arteritis (cTAK) with adult-onset TAK (aTAK).

Methods: Data related to clinical features and response to treatment of patients with cTAK (age of onset <16 years) and aTAK from a large observational cohort in our tertiary care teaching hospital were noted and compared.

Results: Altogether, 602 patients (cTAK = 119; aTAK = 483) were studied. Patients with cTAK had a blunted female: male ratio; but fever, elevated acute phase reactants, involvement of abdominal aorta or its branches, hypertension, abdominal pain, elevated serum creatinine and cardiomyopathy were more common in cTAK as compared with aTAK. Patients with aTAK were more likely to have aortic-arch disease and claudication than cTAK. During follow-up, complete remission was more common in cTAK (87% vs 66%; P < 0.01), but subsequent relapses were equally common (30% vs 27%; P = 0.63). Independent associations of disease duration at presentation with disease extent [Disease Extent Index in TAK (DEI.Tak)] and damage [TAK Damage Score (TADS)] were observed (P ≤ 0.01). Moreover, 54% of patients with symptom duration of >5 years at presentation still continued to have elevated CRP suggesting continued and active inflammation warranting escalation or inititation of immunosuppression.

Conclusion: Patients with cTAK are more likely to have arterial disease below the diaphragm, systemic inflammation and achieve remission. Disease of the aortic arch is more common in patients with aTAK. Longer duration of symptoms prior to initiation of immunosuppression, thereby leading to extensive disease and damage, reflects ongoing disease activity as the rule rather than exception in untreated TAK.
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http://dx.doi.org/10.1093/rheumatology/keaa569DOI Listing
May 2021
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