Publications by authors named "Divya Gupta"

178 Publications

Inactivation of SARS-CoV-2 by β-propiolactone causes aggregation of viral particles and loss of antigenic potential.

Virus Res 2021 Sep 4;305:198555. Epub 2021 Sep 4.

Centre for Cellular and Molecular Biology, Hyderabad 500007, India; Academy for Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

Inactivated viral preparations are important resources in vaccine and antisera industry. Of the many vaccines that are being developed against COVID-19, inactivated whole-virus vaccines are also considered effective. β-propiolactone (BPL) is a widely used chemical inactivator of several viruses. Here, we analyze various concentrations of BPL to effectively inactivate SARS-CoV-2 and their effects on the biochemical properties of the virion particles. BPL at 1:2000 (v/v) concentrations effectively inactivated SARS-CoV-2. However, higher BPL concentrations resulted in the loss of both protein content as well as the antigenic integrity of the structural proteins. Higher concentrations also caused substantial aggregation of the virion particles possibly resulting in insufficient inactivation, and a loss in antigenic potential. We also identify that the viral RNA content in the culture supernatants can be a direct indicator of their antigenic content. Our findings may have important implications in the vaccine and antisera industry during COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.virusres.2021.198555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416322PMC
September 2021

Molecular Evaluation of Low-grade Low-stage Endometrial Cancer With and Without Recurrence.

Int J Gynecol Pathol 2021 Sep 6. Epub 2021 Sep 6.

Department of Pathology and Laboratory Medicine (C.E.M., K.O., S.Motanagh, S.Mirabelli, B.H., L.H.E., J.M.M.) Institute for Computational Biomedicine (K.W.E., P.C., A.S., O.E.); Departments of Obstetrics and Gynecology (S.C.P., D.G., E.C.D., K.H., A.S.); Physiology and Biophysics (A.S.), Weill Cornell Medicine Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian (K.O., K.W.E., P.C., S.M., A.Sigaras, A.Sboner, O.E., L.H.E., J.M.M.) Weill Cornell Medicine (S.M.G.), New York, New York Cancer Genetics Incorporated, Rutherford, New Jersey (B.K.).

Low-grade, low-stage endometrioid carcinomas (LGLS EC) demonstrate 5-yr survival rates up to 95%. However, a small subset of these tumors recur, and little is known about prognostic markers or established mutation profiles associated with recurrence. The goal of the current study was to identify the molecular profiles of the primary carcinomas and the genomic differences between primary tumors and subsequent recurrences. Four cases of LGLS EC with recurrence and 8 cases without recurrence were evaluated via whole-exome sequencing. Three of the 4 recurrent tumors were evaluated via Oncomine Comprehensive Assay. The resulting molecular profiles of the primary and recurrent tumors were compared. Two of the 3 recurrent cases showed additional mutations in the recurrence. One recurrent tumor included an additional TP53 mutation and the other recurrent tumor showed POLE and DDR2 kinase gene mutation. The POLE mutation occurred outside the exonuclease domain. PIK3CA mutations were detected in 4 of 4 primary LGLS EC with recurrence and in 3 of 8 disease-free cases. LGLS EC with recurrence showed higher MSIsensor scores compared with LGLS without recurrence. The level of copy number gains in LGLS EC with recurrence was larger than LGLS EC without recurrence. This pilot study showed 1 of 3 recurrent cases gained a mutation associated with genetic instability (TP53) and 1 of them also acquired a mutation in the DDR2 kinase, a potential therapeutic target. We also noted a higher level of copy number gains, MSIsensor scores and PIK3CA mutations in the primary tumors that later recurred.
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http://dx.doi.org/10.1097/PGP.0000000000000798DOI Listing
September 2021

Antiarthritic activity of OA-DHZ; a gastroprotective NF-κB/MAPK/COX inhibitor.

Cytokine 2021 Aug 26;148:155688. Epub 2021 Aug 26.

Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, India; PK-PD Toxicology and Formulation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, Jammu and Kashmir 180001, India. Electronic address:

Arthritis, a primary autoimmune disorder having a global incidence of 2.03% person/year, is presently being treated by many commercially available drugs that treat symptomatically or improve the disease's clinical state; however, all the therapies pose varying amount of side effects. Therefore, it has become a fundamental need to search for therapeutics that offer better efficacy and safety profile, and the natural or nature-derived products are known for their outstanding performance in this arena. OA-DHZ, known to possess anti-inflammatory and analgesic properties, when explored for its efficacy against arthritis in adjuvant-induced arthritis (AIA) model, was found to inhibit paw edema by 34% and TNF-α, IL-6, and IL-1β by 67%, 39%, and 45% respectively when compared to diseased control. It was also able to reduce the inflamed spleen size by 45% and successfully normalized biochemical and hematological changes that followed arthritis. In vitro studies revealed that the underlying mechanism for inhibiting arthritis progression might be due to NF-κB /MAPK pathway modulation. OA-DHZ also showed selective inhibition of COX-2 in vitro while showing gastroprotective effects when evaluated for ulcerogenic and antiulcer potential in vivo. In contrast to the results obtained from in vivo experimentation, there is a disparity in the pharmacokinetic profile of OA-DHZ, where it showed low oral exposure and high clearance rate. OA-DHZ being antiarthritic acting via NF-κB /MAPK/ COX inhibition while showing gastroprotective effects, can be a suitable candidate to be in the drug pipeline and further exploration.
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http://dx.doi.org/10.1016/j.cyto.2021.155688DOI Listing
August 2021

Edge Caching Based on Collaborative Filtering for Heterogeneous ICN-IoT Applications.

Sensors (Basel) 2021 Aug 15;21(16). Epub 2021 Aug 15.

Department of Computer Science, College of Arts and Science, Prince Sattam Bin Abdul University, Wadi Ad-Dwasir 11991, Saudi Arabia.

The substantial advancements offered by the edge computing has indicated serious evolutionary improvements for the internet of things (IoT) technology. The rigid design philosophy of the traditional network architecture limits its scope to meet future demands. However, information centric networking (ICN) is envisioned as a promising architecture to bridge the huge gaps and maintain IoT networks, mostly referred as ICN-IoT. The edge-enabled ICN-IoT architecture always demands efficient in-network caching techniques for supporting better user's quality of experience (QoE). In this paper, we propose an enhanced ICN-IoT content caching strategy by enabling artificial intelligence (AI)-based collaborative filtering within the edge cloud to support heterogeneous IoT architecture. This collaborative filtering-based content caching strategy would intelligently cache content on edge nodes for traffic management at cloud databases. The evaluations has been conducted to check the performance of the proposed strategy over various benchmark strategies, such as LCE, LCD, CL4M, and ProbCache. The analytical results demonstrate the better performance of our proposed strategy with average gain of 15% for cache hit ratio, 12% reduction in content retrieval delay, and 28% reduced average hop count in comparison to best considered LCD. We believe that the proposed strategy will contribute an effective solution to the related studies in this domain.
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http://dx.doi.org/10.3390/s21165491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402262PMC
August 2021

Pharmacological Activation of Autophagy Restores Cellular Homeostasis in Ultraviolet-(B)-Induced Skin Photodamage.

Front Oncol 2021 2;11:726066. Epub 2021 Aug 2.

Biological Sciences, Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, India.

Ultraviolet (UV) exposure to the skin causes photo-damage and acts as the primary etiological agent in photo-carcinogenesis. UV-B exposure induces cellular damage and is the major factor challenging skin homeostasis. Autophagy allows the fundamental adaptation of cells to metabolic and oxidative stress. Cellular dysfunction has been observed in aged tissues and in toxic insults to cells undergoing stress. Conversely, promising anti-aging strategies aimed at inhibiting the mTOR pathway have been found to significantly improve the aging-related disorders. Recently, autophagy has been found to positively regulate skin homeostasis by enhancing DNA damage recognition. Here, we investigated the geno-protective roles of autophagy in UV-B-exposed primary human dermal fibroblasts (HDFs). We found that UV-B irradiation to HDFs impairs the autophagy response in a time- and intensity-independent manner. However, improving autophagy levels in HDFs with pharmacological activators regulates the UV-B-induced cellular stress by decreasing the induction of DNA photo-adducts, promoting the DNA repair process, alleviating oxidative and ER stress responses, and regulating the expression levels of key cell cycle regulatory proteins. Autophagy also prevents HDFs from UV-B-induced nuclear damage as is evident in TUNEL assay and Acridine Orange/Ethidium Bromide co-staining. Salubrinal (an eIFα phosphatase inhibitor) relieves ER stress response in cells and also significantly alleviates DNA damage and promotes the repair process in UV-B-exposed HDFs. P62-silenced HDFs show enhanced DNA damage response and also disturb the tumor suppressor PTEN/pAKT signaling axis in UV-B-exposed HDFs whereas -silenced HDFs reveal an unexpected consequence by decreasing the UV-B-induced DNA damage. Taken together, these results suggest that interventional autophagy offers significant protection against UV-B radiation-induced photo-damage and holds great promise in devising it as a suitable therapeutic strategy against skin pathological disorders.
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http://dx.doi.org/10.3389/fonc.2021.726066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366585PMC
August 2021

Retinoic Acid Inducible Gene-I like Receptors Activate Snail to Limit RNA Viral Infections.

J Virol 2021 Aug 11:JVI0121621. Epub 2021 Aug 11.

CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad-500007, India.

RLRs are important cytosolic PRRs that sense viral RNA before mounting a response leading to the activation of Type-I IFNs. Several viral infections induce epithelial-mesenchymal transition (EMT), even as its significance remains unclear. Here, we describe that EMT or EMT like process is a general response to viral infections. Our studies identify a previously unknown mechanism of regulation of an important EMT-TF Snail during RNA viral infections, and describe its possible implication. RNA viral infections, poly (I:C) transfection, and ectopic expression of RLR components induced Snail levels, indicating that RLR pathway could regulate its expression. Detailed examination using MAVS-KO cells established that MAVS is essential in this regulation. We identified two ISREs in promoter region and demonstrated that they are important in its transcriptional activation by phosphorylated IRF3. Increasing the levels of Snail activated RLR pathway and dramatically limited replication of RNA viruses DENV, JEV and VSV, pointing to their antiviral functions. Knock-down of Snail resulted in considerable increase in JEV titer, validating its antiviral functions. Finally, TGF-β mediated activation was dependent on Snail levels, confirming its important role in Type-I IFN activation. Thus, EMT-TF Snail is transcriptionally co-regulated with Type-I IFN by RLRs and in turn promotes RLR pathway, further strengthening the antiviral state in the cell. Our work identified an interesting mechanism of regulation of Snail that demonstrates potential co-regulation of multiple innate antiviral pathways triggered by RLRs. Identification of antiviral functions of Snail also provides an opportunity to expand the sphere of RLR signaling. RLRs sense viral genomic RNA or the dsRNA intermediates and trigger the activation of Type I IFNs. Snail transcription factor, commonly associated with epithelial-mesenchymal transition, has been reported to facilitate EMT in several viral infections. Much of these reports come from oncoviruses, leading to the speculation that EMT induced during infection is an important factor in the oncogenesis triggered by these infections. However, our studies reveal that EMT or EMT like processes during viral infections have important functions in antiviral response. We have characterized a new mechanism of transcriptional regulation of Snail by IRF3 through ISRE in their promoters and this finding could have importance in non-viral contexts as well. We also identify that EMT-TF Snail promotes antiviral status of the infected cells through RLR pathway. This work characterizes a new regulatory mechanism of activation of Snail and establishes its unidentified function in antiviral response.
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http://dx.doi.org/10.1128/JVI.01216-21DOI Listing
August 2021

Risk factors for progression or death after first-line platinum-based chemotherapy in real-world patients in the USA with ovarian cancer from 2011 to 2018.

Future Oncol 2021 Aug 11. Epub 2021 Aug 11.

Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine, St Louis, MO 63110, USA.

Patient chart data from the USA during the period of January 2011 through October 2018 were used to assess risk factors for progression in advanced ovarian cancer after response to first-line platinum-based chemotherapy. Patients with stage III/IV ovarian cancer who completed first-line platinum-based chemotherapy after primary or interval debulking surgery were identified from the Flatiron Health database. Cox proportional hazards modeling was used to assess associations between baseline factors and time to next treatment (TTNT) or overall survival (OS). Patients at stage IV or who received interval debulking surgery had shorter TTNT and OS than patients at stage III or who received primary debulking surgery, respectively. OS was worse in patients with residual disease and in wild-type. Multiple factors were associated with shorter TTNT or OS in this retrospective real-world analysis.
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http://dx.doi.org/10.2217/fon-2021-0018DOI Listing
August 2021

Regulation of mitochondrial dynamics in skin: role in pathophysiology.

Int J Dermatol 2021 Aug 7. Epub 2021 Aug 7.

PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, J&K, India.

Skin is a dynamic interface between the external environment and internal organs. It has high turnover that allows the renewal of dead skin cells, thus maintaining a healthy skin homeostasis. Mitochondria fulfills all the energy needs for these cells. In addition, mitochondria are an active source of free radicals that have been determined as crucially important in skin health and disease. The common notion of limited role of mitochondria as merely the cellular powerhouse has drastically changed. Several extracellular stressors have proved to induce impairment in the dynamic properties of mitochondria such as fusion and fission, which further leads to an activation of selective autophagic response known as mitophagy. Altered mitochondrial dynamics have been lately associated with skin photodamage and cutaneous manifestations of several diseased states, thereby suggesting it to be an effective therapeutic target. This review summarizes the molecular mechanisms involved with impaired mitochondrial dynamics and its potential role in skin health and disease.
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http://dx.doi.org/10.1111/ijd.15744DOI Listing
August 2021

Pharmacokinetics and safety of niraparib in patients with moderate hepatic impairment.

Cancer Chemother Pharmacol 2021 Jul 29. Epub 2021 Jul 29.

University of Colorado Cancer Center, Mail Stop C238, 12850 East Montview Blvd., V20-1223, Aurora, CO, 80045, USA.

Purpose: The purpose of this study is to characterize niraparib pharmacokinetics (PK) and safety in patients with normal hepatic function (NHF) versus moderate hepatic impairment (MHI).

Methods: Patients with advanced solid tumors were stratified by NHF or MHI (National Cancer Institute-Organ Dysfunction Working Group criteria [bilirubin > 1.5-3 × upper limit of normal and any aspartate aminotransferase elevation]). In the PK phase, all patients received one 300 mg dose of niraparib. In the extension phase, patients with MHI received niraparib 200 mg daily; patients with NHF received 200 or 300 mg based on weight (< 77 kg, ≥ 77 kg)/platelets (< 150,000/µL, ≥ 150,000/µL). PK parameters included maximum concentration (C), area under the curve to last measured concentration (AUC) and extrapolated to infinity (AUC). Safety was assessed in both phases. Exposure-response (E-R) modeling was used to predict MHI effects on exposure and safety of niraparib doses ≤ 200 mg or 300/200 mg or 200/100 mg weight/platelet regimens.

Results: In the PK phase (NHF, n = 9; MHI, n = 8), mean niraparib C was 7% lower in patients with MHI versus NHF. Mean exposure (AUC, AUC) was increased by 45% and 56%, respectively, in patients with MHI without impacting tolerability. In the extension phase (NHF, n = 8; MHI, n = 7), the overall safety profile was consistent with previous trials. In patients with MHI, E-R modeling predicted niraparib 200 mg reduced Grade ≥ 3 thrombocytopenia incidence, whereas a 200/100 mg regimen yielded exposures below efficacy-associated levels in 15% of patients.

Conclusion: These findings support adjusting the 300 mg niraparib starting dose to 200 mg QD in patients with MHI.

Trial Registration: NCT03359850; registered December 2, 2017.
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http://dx.doi.org/10.1007/s00280-021-04329-8DOI Listing
July 2021

Repeated cross-sectional analysis of hydroxychloroquine deimplementation in the AHA COVID-19 CVD Registry.

Sci Rep 2021 07 23;11(1):15097. Epub 2021 Jul 23.

Center for Innovation and Value at Parkland, University of Texas Southwestern Medical Center, Dallas, TX, USA.

There is little data describing trends in the use of hydroxychloroquine for COVID-19 following publication of randomized trials that failed to demonstrate a benefit of this therapy. We identified 13,957 patients admitted for active COVID-19 at 85 U.S. hospitals participating in a national registry between March 1 and August 31, 2020. The overall proportion of patients receiving hydroxychloroquine peaked at 55.2% in March and April and decreased to 4.8% in May and June and 0.8% in July and August. At the hospital-level, median use was 59.4% in March and April (IQR 48.5-71.5%, range 0-100%) and decreased to 0.3% (IQR 0-5.4%, range 0-100%) by May and June and 0% (IQR 0-1.3%, range 0-36.4%) by July and August. The rate and hospital-level uniformity in deimplementation of this ineffective therapy for COVID-19 reflects a rapid response to evolving clinical information and further study may offer strategies to inform deimplementation of ineffective clinical care.
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http://dx.doi.org/10.1038/s41598-021-94203-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302649PMC
July 2021

Engineering skeletal muscle tissues with advanced maturity improves synapse formation with human induced pluripotent stem cell-derived motor neurons.

APL Bioeng 2021 Sep 13;5(3):036101. Epub 2021 Jul 13.

Department of Biological Sciences, Dornsife College of Arts and Letters, University of Southern California, Los Angeles, California 90089, USA.

To develop effective cures for neuromuscular diseases, human-relevant models of neuromuscular tissues are critically needed to probe disease mechanisms on a cellular and molecular level. However, previous attempts to co-culture motor neurons and skeletal muscle have resulted in relatively immature neuromuscular junctions (NMJs). In this study, NMJs formed by human induced pluripotent stem cell (hiPSC)-derived motor neurons were improved by optimizing the maturity of the co-cultured muscle tissue. First, muscle tissues engineered from the C2C12 mouse myoblast cell line, cryopreserved primary human myoblasts, and freshly isolated primary chick myoblasts on micromolded gelatin hydrogels were compared. After three weeks, only chick muscle tissues remained stably adhered to hydrogels and exhibited progressive increases in myogenic index and stress generation, approaching values generated by native muscle tissue. After three weeks of co-culture with hiPSC-derived motor neurons, engineered chick muscle tissues formed NMJs with increasing co-localization of pre- and postsynaptic markers as well as increased frequency and magnitude of synaptic activity, surpassing structural and functional maturity of previous models. Engineered chick muscle tissues also demonstrated increased expression of genes related to sarcomere maturation and innervation over time, revealing new insights into the molecular pathways that likely contribute to enhanced NMJ formation. These approaches for engineering advanced neuromuscular tissues with relatively mature NMJs and interrogating their structure and function have many applications in neuromuscular disease modeling and drug development.
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http://dx.doi.org/10.1063/5.0054984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282350PMC
September 2021

A Comparative Evaluation of Oral Clonidine, Dexmedetomidine, and Melatonin As Premedicants in Pediatric Patients Undergoing Subumbilical Surgeries.

Rom J Anaesth Intensive Care 2020 Jul 10;27(1):35-42. Epub 2020 Aug 10.

Department of Surgery, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand.

Introduction: Sedative premedication is the mainstay of pharmacological therapy in children undergoing surgeries. This study compares preoperative melatonin, clonidine, and dexmedetomidine on sedation, ease of anesthesia induction, emergence delirium, and analgesia.

Materials And Methods: One hundred and five children, 3-8 years, either sex, ASA I/II, posted for infraumbilical surgery, randomized to receive clonidine 5 mcg/kg (Group C), dexmedetomidine 3 mcg/kg (Group D), and melatonin 0.2 mg/kg (Group M) 45 minutes before surgery. Preoperative Sedation/Anxiety and Child-Parent Separation Score (CPSS) were assessed. Identical anesthesia technique was utilized. Emergence delirium (Watcha score) and postoperative pain (Objective Pain Scale score) were monitored postoperatively.

Results: Patients were demographically comparable. Sedation score >Grade 3 was absent. Grades 1/2/3 were present in 10/19/6 (Group C), 2/26/7 (Group D), and 7/26/2 (Group M). Grade 1 CPSS was present in 42.6% (Group C), 37.1% (Group D), and 28.6% (Group M). Pediatric Anesthesia Behavior Score (PABS) was comparable between Groups C and D (p = 0.224; 95% CI -0.090 to 0.604) and Groups C and M (p = 0.144; 95% CI -0.633 to 0.061) while PABS was better in Group D compared to Group M (p = 0.0007; 95% CI -0.890 to -0.195). Watcha scores were 33/2/0/0 (Group C), 34/1/0/0 (Group D), and 32/2/1/0 (Group M) immediately after extubation. Scores were 31/4/0/0 (Group C), 33/2/0/0 (Group D), and 31/4/0/0 (Group M) at 30 minutes and 28/7/0/0 (Group C), 29/6/0/0 (Group D), and 24/11/0/0 (Group M) at 1 hour. The scores were comparable (p > 0.05). Objective Pain Scale scores were comparable between Groups C and D and Groups C and M (p > 0.05). Lower scores were present in Group D compared to M (p = 0.023).

Conclusion: Melatonin, clonidine, and dexmedetomidine are efficacious for producing preoperative sedation, reducing anxiety, postoperative pain, and emergence delirium.
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http://dx.doi.org/10.2478/rjaic-2020-0006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158305PMC
July 2020

A Randomized Clinical Trial on Anterior Approach vs Conventional Hepatectomy for Resection of Colorectal Liver Metastasis-To Terminate or Not to Terminate the Study.

JAMA Surg 2021 Sep;156(9):893-894

Department of Medicine, Stanford University School of Medicine, VA Palo Alto Health Care System, Palo Alto, California.

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http://dx.doi.org/10.1001/jamasurg.2021.1800DOI Listing
September 2021

Intravenous Clonidine versus Intraperitoneal Clonidine for Postoperative Analgesia After Total Abdominal Hysterectomy: A Randomised Controlled Trial.

Turk J Anaesthesiol Reanim 2021 Apr 30;49(2):118-123. Epub 2020 Nov 30.

Department of Anaesthesiology and Intensive Care, Maulana Azad Medical College, Delhi, India.

Objective: This prospective randomised double-blind study was conducted to compare the effect of intravenous (IV) with intraperitoneal (IP) administration of clonidine with respect to analgesic efficacy and side effects.

Methods: A total of 60 American Society of Anaesthesiologists (ASA) physical status class I and II patients, aged 35-60 years, undergoing total abdominal hysterectomy, were randomly divided into 2 groups. Standard general anaesthesia technique was used. All the patients in group IV received 3 μg kg of IV clonidine after resection of the uterus along with 0.25% bupivacaine (20 mL intraperitoneally and 10 mL as wound infiltration), whereas patients in group IP received 10 mL of normal saline intravenously and 3 μg kg of clonidine mixed with 0.25% bupivacaine (20 mL intraperitoneally and 10 mL as wound infiltration). Postoperative analgesia was provided with IV diclofenac every 8 hours and IV fentanyl (1 μg kg) on demand. Pain at rest, opioid consumption, level of sedation and severity of nausea were recorded for 24 hours. The heart rate (HR) and blood pressure (BP) were recorded at an interval of 15 minutes for 2 hours followed by routine hourly monitoring.

Results: Both the groups were found to be similar with respect to demography and ASA physical status. The maximum pain was felt at 6 hours in both the groups. The mean visual analogue scale score at 6 hours (p=0.47) was comparable. However, patients in group IV had significantly higher sedation (p<0.001) and nausea (p=0.013) scores on arrival at post-anaesthesia care unit along with a significant reduction in HR (p=0.001) and BP (p=0001) for the first 2 hours postoperatively.

Conclusion: Although IP clonidine is comparable with IV clonidine with respect to postoperative pain scores and supplementary opioid requirement, the side effects are significantly less with IP clonidine.
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http://dx.doi.org/10.5152/TJAR.2020.55938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098739PMC
April 2021

Glabridin ameliorates methotrexate-induced liver injury via attenuation of oxidative stress, inflammation, and apoptosis.

Life Sci 2021 Aug 4;278:119583. Epub 2021 May 4.

PK-PD, Toxicology and Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India. Electronic address:

Despite unprecedented advances in modern medicine, no safe and effective drug is available to date for oral administration to combat drug-induced liver injury, which is a vital concern nowadays. The present study deals with the hepatoprotective effect of pure glabridin, a key phytoconstituent from Glycyrrhiza glabra with mechanistic investigations using an in-vivo methotrexate-induced liver injury model as there is no such precedent. The study was performed in the Swiss mice model where a single dose of methotrexate (40 mg/kg) was given on the 7 day through an intraperitoneal route to induce hepatotoxicity, and glabridin as a test compound was administered orally for eleven consecutive days at 10 to 40 mg/kg. Glabridin markedly improved serum biochemical parameters (SGPT, SGOT), proinflammatory cytokine (TNF-α) level, oxidative stress markers (MDA, GSH, SOD, CAT) as compared to methotrexate alone. Alterations in methotrexate-induced liver architecture were considerably prevented by glabridin treatment as suggested by liver histopathological examination and SEM investigation. Glabridin substantially prevented methotrexate-induced down-regulation of Nrf2, & activation of NF-κB, and caused up-regulation of BAX at different dose levels. Overall, glabridin is found to protect methotrexate-induced hepatotoxicity by improving important factors for oxidative stress, inflammation, and apoptosis.
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http://dx.doi.org/10.1016/j.lfs.2021.119583DOI Listing
August 2021

Respiratory-related leg movements vs periodic limb movements in sleep: a scoring conundrum. an editorial.

Sleep Med 2021 05 21;81:98-100. Epub 2020 Nov 21.

Hackensack-Meridian Health-JFK University Medical Center, 65 James Street, Edison NJ 08820, USA.

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http://dx.doi.org/10.1016/j.sleep.2020.11.016DOI Listing
May 2021

The Cardiovascular Quality Improvement and Care Innovation Consortium: Inception of a Multicenter Collaborative to Improve Cardiovascular Care.

Circ Cardiovasc Qual Outcomes 2021 01 12;14(1):e006753. Epub 2021 Jan 12.

University of Colorado School of Medicine, Aurora (P.M.H.).

Despite decades of improvement in the quality and outcomes of cardiovascular care, significant gaps remain. Existing quality improvement strategies are often limited in scope to specific clinical conditions and episodic care. Health services and outcomes research is essential to inform gaps in care but rarely results in the development and implementation of care delivery solutions. Although individual health systems are engaged in projects to improve the quality of care delivery, these efforts often lack a robust study design or implementation evaluation that can inform generalizability and further dissemination. Aligning the work of health care systems and health services and outcomes researchers could serve as a strategy to overcome persisting gaps in cardiovascular quality and outcomes. We describe the inception of the Cardiovascular Quality Improvement and Care Innovation Consortium that seeks to rapidly improve cardiovascular care by (1) developing, implementing, and evaluating multicenter quality improvement projects using innovative care designs; (2) serving as a resource for quality improvement and care innovation partners; and (3) establishing a presence within existing quality improvement and care innovation structures. Success of the collaborative will be defined by projects that result in changes to care delivery with demonstrable impacts on the quality and outcomes of care across multiple health systems. Furthermore, insights gained from implementation of these projects across sites in Cardiovascular Quality Improvement and Care Innovation Consortium will inform and promote broad dissemination for greater impact.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006753DOI Listing
January 2021

Characterization of Gelatin Hydrogels Cross-Linked with Microbial Transglutaminase as Engineered Skeletal Muscle Substrates.

Bioengineering (Basel) 2021 Jan 6;8(1). Epub 2021 Jan 6.

Laboratory for Living Systems Engineering, Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089, USA.

Engineered in vitro models of skeletal muscle are essential for efficiently screening drug safety and efficacy. However, conventional culture substrates poorly replicate physical features of native muscle and do not support long-term culture, which limits tissue maturity. Micromolded gelatin hydrogels cross-linked with microbial transglutaminase (gelatin-MTG hydrogels) have previously been shown to induce C21C2 myotube alignment and improve culture longevity. However, several properties of gelatin-MTG hydrogels have not been systematically characterized, such as changes in elastic modulus during incubation in culture-like conditions and their ability to support sarcomere maturation. In this study, various gelatin-MTG hydrogels were fabricated and incubated in ambient or culture-like conditions. Elastic modulus, mass, and transmittance were measured over a one- or two-week period. Compared to hydrogels in phosphate buffered saline (PBS) or ambient air, hydrogels in Dulbecco's Modified Eagle Medium (DMEM) and 5% CO demonstrated the most stable elastic modulus. A subset of gelatin-MTG hydrogels was micromolded and seeded with C2C12 or primary chick myoblasts, which aligned and fused into multinucleated myotubes with relatively mature sarcomeres. These data are important for fabricating gelatin-MTG hydrogels with predictable and stable mechanical properties and highlight their advantages as culture substrates for engineering relatively mature and stable muscle tissues.
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http://dx.doi.org/10.3390/bioengineering8010006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825108PMC
January 2021

Investigation on hydrochar and macromolecules recovery opportunities from food waste after hydrothermal carbonization.

Sci Total Environ 2020 Dec 12;749:142294. Epub 2020 Sep 12.

Environmental Science and Engineering Department, Indian Institute of Technology (IIT) Bombay, Mumbai 400076, India. Electronic address:

In this paper, the performance of hydrothermal carbonization (HTC) was investigated on real food waste (FW) to improve resource recovery opportunities. The HTC was performed in a high pressure batch reactor (without addition of water) at desired temperatures for different durations to study the properties of solid hydrochar (HC) and process water (PW) produced during the process. The reaction temperature and run time of 200 °C and 1 h, respectively were found suitable to produce the HC (high heating value = ~30 MJ/kg) having properties similar to that of the peat/lignite coal. Moreover, durable pellets could also be prepared from HC without addition of binder. The kinetic constants for HC combustion were also predicted using non-isothermal model-free approach for the data obtained from thermo-gravimetric analysis. In the PW samples recovered after HTC, several value-added compounds like 2,5-hydroxymethyl furfural, humic-like substances (HLS), proteins, carbohydrates and volatile fatty acids could be detected in appreciable quantities. However, longer reaction resulted in further degradation of above macromolecules into VFAs. Based on the observations, a pathway for FW degradation during HTC process is proposed. Moreover, the HLS and proteins mixture recovered from the PW sample exhibited no adverse impact on seed growth. The present study demonstrates that the HTC can be a potential treatment method for FW to recover a variety of useful materials. Further studies should focus on developing cost-effective methods for the recovery of various macromolecules from PW.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142294DOI Listing
December 2020

Inhibition of Ultraviolet-B Radiation Induced Photodamage by Trigonelline Through Modulation of Mitogen Activating Protein Kinases and Nuclear Factor-κB Signaling Axis in Skin.

Photochem Photobiol 2021 Jul 9;97(4):785-794. Epub 2021 Feb 9.

Pharmacokinetics - Pharmacodynamics and Toxicology Division, Council of Scientific and Industrial Research-Indian Institute of Integrative Medicine, Jammu, India.

Cutaneous photodamage is incited via exposure of ultraviolet-B (UV-B) radiation to skin, characterized by the manifestation of oxidative stress, inflammation, collagen degradation and apoptosis which translates to external aging signs such as wrinkle formation and leathery skin appearance. Meanwhile, it increases cellular susceptibility to photocarcinogenesis. Several studies have accumulated evidence regarding the usage of natural agents in reversing the clinical signs of photoaging as well as preventing photo-toxicity at molecular level. In this study, we have explored the therapeutic potential of natural agent Trigonelline (TG) against UV-B radiation mediated skin photodamage. Various parameters modulated by the exposure of UV-B radiation were investigated in human skin cells and chronic photodamage mice model (Balb/c). We found that TG alleviates UV-B radiation induced photodamage in human skin cells and Balb/c skin mice. TG treatment in UV-B irradiated skin cells abates UV-B radiation mediated phototoxicity, oxidative stress, inflammation and apoptosis. At molecular level, we observed TG treatment significantly prevents the reactive oxygen species (ROS) generation and lipid peroxidation, restores collagen synthesis and matrix metalloproteinase (MMPs) levels. The in vitro findings were replicated in the in vivo model. We found that the TG acts potentially via modulation of ROS-MAPKs-NF-κB axis. Collectively, we propose that TG acts antagonistically against UV-B mediated skin damage and has strong potential to be developed as a therapeutic and cosmetical agent against photodamage disorders.
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http://dx.doi.org/10.1111/php.13369DOI Listing
July 2021

Managing COVID-19-positive Solid Organ Transplant Recipients in the Community: What a Community Healthcare Provider Needs to Know.

Transplant Direct 2020 Dec 16;6(12):e633. Epub 2020 Nov 16.

Emory Transplant Center, Emory University School of Medicine, Atlanta, GA.

Background: The current surge of coronavirus 2019 (COVID-19) cases in certain parts of the country has burdened the healthcare system, limiting access to tertiary centers for many. As a result, COVID-19-positive Solid Organ Transplant (SOT) recipients are increasingly being managed by local healthcare providers. It is crucial for community providers to understand disease severity and know if COVID-19-impacted SOT recipients have a different clinical course compared with COVID-19-negative SOT recipients with a similar presentation.

Methods: We conducted a retrospective analysis on SOT recipients suspected to have COVID-19 infection tested during March 14, 2020-April 30, 2020. Patients were followed from time of testing to May 31, 2020.

Results: One hundred sixty SOT recipients underwent testing: 22 COVID-19 positive and 138 COVID-19 negative. COVID-19-positive patients were more likely to have rapid progression of symptoms (median 3 vs 6 d, = 0.002), greater hospitalizations (78% vs 64%, < 0.017), and need for intensive care unit care (45% vs 17%, < 0.001) Severe COVID-19 infection was not observed in patients on Belatacept for immunosuppression (30% vs 87%, = 0.001). COVID- 19 positive patients in the intensive care unit were more likely to have multifocal opacities on radiological imaging in comparison to those admitted to the medical floor (90% vs 11%). Survival probability was similar in both cohorts.

Conclusion: COVID-19-infected SOT recipients have a propensity for rapid clinical decompensation. Local providers need to be work closely with transplant centers to appropriately triage and manage COVID-19 SOT recipients in the community.
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http://dx.doi.org/10.1097/TXD.0000000000001074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673773PMC
December 2020

A comparative evaluation of the antibacterial efficacy of , and 5% sodium hypochlorite against : An study.

J Conserv Dent 2020 Jan-Feb;23(1):97-101. Epub 2020 Oct 10.

Department of Pharmacology, Bharati Vidyapeeth (Deemed to be) University Medical College and Hospital, Sangli, Maharashtra, India.

Objectives: The aim of this study is to evaluate and compare the antibacterial efficacy of , and 5% sodium hypochlorite against .

Methodology: Herbal extracts of and were prepared. Tryptone soya broth was used to grow and agar plates were prepared. The tested solutions (Group A: 5% NaOCl, Group B: 20% , Group C: 12.5% , Group D: 10% , Group E: 10% ) were added to the wells made on agar media. Agar diffusion test was performed. Plates were incubated at 37°C for 24 h. Bacterial zones of inhibition were recorded.

Results: The data were analyzed statistically by Analysis of Variance (ANOVA) and comparison by Tukey's -test. The highest zone of inhibition against was shown by 5% NaOCl, followed by 10% , 20% and 10% showed similar comparable antibacterial activity. The least zone of inhibition was showed by S. persica.

Conclusion: 5% NaOCl showed the maximum antibacterial activity, and herbal products demonstrated significant antibacterial activity against and can be employed as an alternative to NaOCl.
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http://dx.doi.org/10.4103/JCD.JCD_48_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657435PMC
October 2020

Racial and Ethnic Differences in Presentation and Outcomes for Patients Hospitalized With COVID-19: Findings From the American Heart Association's COVID-19 Cardiovascular Disease Registry.

Circulation 2021 06 17;143(24):2332-2342. Epub 2020 Nov 17.

Duke Clinical Research Institute, Duke University, Durham, NC (N.S., D.H., R.A.M., T.Y.W.).

Background: The coronavirus disease 2019 (COVID-19) pandemic has exposed longstanding racial and ethnic inequities in health risks and outcomes in the United States. We aimed to identify racial and ethnic differences in presentation and outcomes for patients hospitalized with COVID-19.

Methods: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7868 patients by race/ethnicity treated at 88 hospitals across the United States between January 17, 2020, and July 22, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events (death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization alone. Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital.

Results: Among 7868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios for mortality were 0.93 (95% CI, 0.76-1.14) for Black patients, 0.90 (95% CI, 0.73-1.11) for Hispanic patients, and 1.31 (95% CI, 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median odds ratio across hospitals was 1.99 (95% CI, 1.74-2.48). Results were similar for major adverse cardiovascular events. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted odds ratio, 1.48 [95% CI, 1.16-1.90]).

Conclusions: Although in-hospital mortality and major adverse cardiovascular events did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity because of their disproportionate representation among COVID-19 hospitalizations.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126640PMC
June 2021

Disseminated Kaposi's sarcoma as a presenting sign of HIV in an Indian male: A case report with dermoscopic findings.

Indian J Sex Transm Dis AIDS 2020 Jan-Jun;41(1):102-105. Epub 2020 Jun 18.

Department of Pathology, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India.

Kaposi's sarcoma (KS) is one of the AIDS-defining illnesses, which tends to occur at low CD4 count. It is the most common malignancy associated with HIV disease. Yet, there is a paucity of Indian case reports of KS in the English literature. We report the case of a 45-year-old HIV-positive heterosexual male with an unusual presentation of KS in the form of unilateral lymphedema mimicking cellulitis. We also describe the dermoscopic findings of the same.
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http://dx.doi.org/10.4103/ijstd.IJSTD_53_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529162PMC
June 2020

Cost-Effectiveness of Initial Versus Delayed Lanreotide for Treatment of Metastatic Enteropancreatic Neuroendocrine Tumors.

J Natl Compr Canc Netw 2020 09;18(9):1200-1209

Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut.

Background: The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors.

Methods: We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide's cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses.

Results: Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide's price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained.

Conclusions: At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.
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http://dx.doi.org/10.6004/jnccn.2020.7563DOI Listing
September 2020

Optical Clearing of Skeletal Muscle Bundles Engineered in 3-D Printed Templates.

Ann Biomed Eng 2021 Feb 3;49(2):523-535. Epub 2020 Aug 3.

Laboratory for Living Systems Engineering, Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA, 90089, USA.

Many techniques for engineering and interrogating three-dimensional (3-D) muscle bundles from animal- or patient-derived myoblasts have recently been developed to overcome the limitations of existing in vitro and in vivo model systems. However, many approaches for engineering 3-D muscle bundles rely on specialized and time-consuming techniques, such as photolithography for fabrication and cryosectioning for histology. Cryosectioning also limits visualization to a single plane instead of the entire 3-D structure. To address these challenges, we first implemented a consumer-grade 3-D-printer to rapidly prototype multiple templates for engineering muscle bundles. We then employed our templates to engineer 3D muscle bundles and identify template geometries that promoted bundle survival over three weeks. Subsequently, we implemented tissue clearing, immunostaining, and confocal imaging to acquire z-stacks of intact muscle bundles labelled for myogenic markers. With this approach, we could select the imaging plane on-demand and visualize the intact 3-D structure of bundles. However, tissue clearing did cause some tissue degradation that should be considered. Together, these advances in muscle tissue engineering and imaging will accelerate the use of these 3-D tissue platforms for disease modeling and therapeutic discovery.
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http://dx.doi.org/10.1007/s10439-020-02583-0DOI Listing
February 2021

Nano-scale depth-varying recrystallization of oblique Ar sputtered Si(111) layers.

Sci Rep 2020 Jul 17;10(1):11905. Epub 2020 Jul 17.

Department of Physics, Kurukshetra University, Kurukshetra, 136119, India.

Silicon, the workhorse of semiconductor industry, is being exploited for various functional applications in numerous fields of nanotechnology. In this paper, we report the fabrication of depth controllable amorphous silicon (a-Si) layers under 80 keV Ar ion sputtering at off-normal ion incidences of 30°, 40° and 50° and crystallization of these amorphous Si(111) layers under thermal annealing. We find that the irradiated samples were not fully amorphized even for the lowest oblique incidence of 30°. Sputtering at off-normal incidences induces depth controllable surface amorphization in Si(111). Annealing at temperature of 1,073 K is characterized by formation of depth-varying buried amorphous layer due to defect recrystallization and damage recovery. Some remnant tensile stress has been observed for recrystallized samples even for lowest oblique incidence. The correlation of amorphization and stress due to sputtering induced by oblique incidence has been discussed systematically. The possible mechanism of recrystallization is discussed in terms of vacancies produced in sputtering dominated regime and their migration during annealing treatment. Our results reveal that with appropriate selection of oblique ion beam sputtering parameters, depth controllable surface amorphization and recrystallization may be fine-tuned to achieve co-existing amorphous and crystalline phases, playing a crucial role in fabrication of substrates for IC industry.
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http://dx.doi.org/10.1038/s41598-020-68873-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367853PMC
July 2020

Glutathione S-transferase: a versatile protein family.

3 Biotech 2020 Jul 27;10(7):321. Epub 2020 Jun 27.

Faculty of Bioscience, Institute of Bioscience and Technology, Shri Ramswaroop Memorial University, Lucknow-Deva Road, Barabanki, Uttar Pradesh India.

Glutathione-S transferase (GST) is a most ancient protein superfamily of multipurpose roles and evolved principally from gene duplication of an ancestral GSH binding protein. They have implemented in diverse plant functions such as detoxification of xenobiotic, secondary metabolism, growth and development, and majorly against biotic and abiotic stresses. The vital structural features of GSTs like highly divergent functional topographies, conserved integrated architecture with separate binding pockets for substrates and ligand, the stringent structural fidelity with high Tm values (50º-60º), and stress-responsive cis-regulatory elements in the promoter region offer this protein as most flexible plant protein for plant breeding approaches, biotechnological applications, etc. This review article summarizes the recent information of GST evolution, and their distribution and structural features with emphasis on the assorted roles of Ser and Cys GSTs with the signature motifs in their active sites, alongside their recent biotechnological application in the area of agriculture, environment, and nanotechnology have been highlighted.
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http://dx.doi.org/10.1007/s13205-020-02312-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320970PMC
July 2020

Sacubitril/Valsartan in Advanced Heart Failure With Reduced Ejection Fraction: Rationale and Design of the LIFE Trial.

JACC Heart Fail 2020 10 10;8(10):789-799. Epub 2020 Jun 10.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients ≥18 years of age with advanced HF, defined as an EF ≤35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/ml), and ≥1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736).
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http://dx.doi.org/10.1016/j.jchf.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286640PMC
October 2020

Audit on Practices of Stress Ulcer Prophylaxis in Intensive Care Unit Patients.

Indian J Crit Care Med 2020 Mar;24(3):160-167

Department of Anaesthesiology and Critical Care, Maulana Azad Medical College, New Delhi, India.

Background: This audit was aimed at studying current practices regarding the use of stress ulcer prophylaxis (SUP) in the Indian critical care setup, with the background aim of raising awareness regarding the use and indications of SUP in critically ill patients.

Materials And Methods: After registering the trial with the clinical trial registry, India, a structured audit questionnaire containing 26 questions pertaining to SUP was distributed through electronic media among clinicians working in the intensive care units (ICUs) across India. Responses obtained were statistically analyzed.

Results: The questionnaire was sent to 550 clinicians. Only 197 responded, of whom 91.4% were anesthesiologists, 5.6% were physicians, and 3% were intensivists. The audit revealed that 33% respondents were unaware of the existing SUP guidelines and around 32% did not have protocols for SUP in their ICU. Sixty-nine percent of respondents felt that all ICU patients must receive SUP and 44.7% opined that it should be started on ICU arrival. Almost 94% knew that early enteral feeding is protective against stress ulceration. Only 24.9% responders agreed that there must be clear indications for SUP, and most of them were unaware of all the potential side effects. Once initiated, 43.7% respondents would stop prophylaxis when no indication was left, whereas 69 respondents would stop on ICU discharge.

Conclusion: There is a lack of awareness regarding initiation, choice of agent, adverse effects as well as termination of SUP in ICU and guidelines for the same. Institutional protocols should be in place and steps need to be taken to prevent unwarranted use.

How To Cite This Article: Gupta D, Bhalotra AR, Singh R. Audit on Practices of Stress Ulcer Prophylaxis in Intensive Care Unit Patients. Indian J Crit Care Med 2020;24(3):160-167.
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http://dx.doi.org/10.5005/jp-journals-10071-23368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225769PMC
March 2020
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