Publications by authors named "Sharma Ankur"

191 Publications

Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates.

NPJ Vaccines 2022 Jan 21;7(1). Epub 2022 Jan 21.

Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, USA.

Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.
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http://dx.doi.org/10.1038/s41541-022-00436-6DOI Listing
January 2022

An unusual case of recurrent subdural hematoma.

Acta Neurol Taiwan 2022 Sep 18. Epub 2022 Sep 18.

Department of Anesthesia and Critical Care, AIIMS, Jodhpur.

Purpose: We here report an uncommon cause of recurrent subdural hematoma in a female with thrombocytopenia.

Case Report: The patients'detailed workup revealed a diagnosis of chronic disseminated intravascular coagulation. Subsequently, her bone marrow biopsy indicated bone marrow suppression and computed tomography of the abdomen showed carcinoma of the gallbladder with vertebral metastasis.

Conclusion: If a patient present with recurrent subdural hematoma, adequate investigations and timely management should be pursued to avoid further complications.
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September 2022

Plasma neutrophil gelatinase-associated lipocalin and Interleukin-18 as predictors of acute kidney injury in renal transplant recipients: A pilot study.

Saudi J Kidney Dis Transpl 2021 Mar-Apr;32(2):355-363

Department of Biochemistry, Institute of Liver and Biliary Sciences, New Delhi, India.

Urine neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL- 18) have shown promise for predicting renal graft recovery. However, urinary flow rate variations may cause variable biomarker dilution. Plasma NGAL and IL-18 may form a biomarker panel that may help predict delayed graft function and slow graft function (SGF) in renal transplant recipients within the first two postoperative days earlier than serum creatinine. There are only a few studies in the literature using plasma NGAL for predicting renal graft recovery. Hence, we planned this study. This observational single-center, prospective cohort study was conducted in renal transplant recipients above 18 years of age. In 22 consecutive renal transplant recipients, we collected ethylenediaminetetraacetic acid-plasma samples 1 h before surgery and subsequently at 6 h, 24 h, and 48 h after surgery for NGAL and IL-18 by sandwich enzyme-linked immuno-sorbent assay technique. Serum creatinine was measured as a part of routine transplant protocol. In renal transplant recipients, neither serum levels of NGAL and IL-18 nor their trends could reliably predict SGF. The only significant correlation existed between serum creatinine at day 2 and IL-18 at day 2 with P = 0.023. Serum NGAL did not correlate with serum creatinine in this setting of renal transplantation. Patients with immediate graft function had a greater percentage decrease of creatinine at day 1 and day 2 (P = 0.002 and 0.001) The percentage change in IL-18 at 24 h and 48 h after transplant from baseline could predict the occurrence of early graft loss (EGL) (P = 0.05, 0.04). The cutoffs were -4.12% at day 1 and +3.39% at day 2 with area under receiver operator characteristics of 0.82 and 0.83, respectively. The percentage change in IL-18 may be a useful marker of EGL in renal transplant recipients. Serum NGAL and creatinine were not able to predict EGL.
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http://dx.doi.org/10.4103/1319-2442.335447DOI Listing
January 2022

Opium Addiction: Practical Issues in ICU.

Indian J Crit Care Med 2021 Sep;25(9):1082-1083

Department of Anaesthesiology and Critical Care, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Das AK, Sharma A, Kothari N, Goyal S. Opium Addiction: Practical Issues in ICU. Indian J Crit Care Med 2021;25(9):1082-1083.
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http://dx.doi.org/10.5005/jp-journals-10071-23939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664020PMC
September 2021

Selective Targeting of the Novel CK-10 Nanoparticles to the MDA-MB-231 Breast Cancer Cells.

J Pharm Sci 2021 Dec 17. Epub 2021 Dec 17.

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, South Valley University, Qena, Egypt. Electronic address:

The main objective of this project was to formulate novel decorated amphiphilic PLGA nanoparticles aiming for the selective delivery of the novel peptide (CK-10) to the cancerous/tumor tissue. Novel modified microfluidic techniques were used to formulate the nanoparticles. This technique was modified by using of Nano Assemblr associated with salting out of the organic solvent using KHPO. This modification is associated with higher peptide loading efficiencies, smaller size and higher uniformity. Size, zeta potential & qualitative determination of the adsorbed targeting ligands were measured by dynamic light scattering and laser anemometry techniques using the zeta sizer. Quantitative estimation of the adsorbed targeting ligands was done by colorimetry and spectrophotometric techniques. Qualitative and quantitative uptakes of the various PLGA nanoparticles were examined by the fluorescence microscope and the flow cytometer while the cytotoxic effect of the nanoparticles was measured by the colorimetric MTT assay. PLGA/poloxamer.FA, PLGA/poloxamer.HA, and PLGA/poloxamer.Tf have breast cancer MDA. MB321 cellular uptakes 83.8, 75.43 & 69.37 % which are higher than those of the PLGA/B cyclodextrin.FA, PLGA/B cyclodextrin.HA and PLGA/B cyclodextrin.Tf 80.87, 74.47 & 64.67 %. Therefore, PLGA/poloxamer.FA and PLGA/poloxamer.HA show higher cytotoxicity than PLGA/ poloxamer.Tf with lower breast cancer MDA-MB-231 cell viabilities 30.74, 39.15 & 49.23 %, respectively. The design of novel decorated amphiphilic CK-10 loaded PLGA nanoparticles designed by the novel modified microfluidic technique succeeds in forming innovative anticancer formulations candidates for therapeutic use in aggressive breast cancers.
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http://dx.doi.org/10.1016/j.xphs.2021.12.014DOI Listing
December 2021

Mucormycosis: A Case Series of Patients Admitted in Non-COVID-19 Intensive Care Unit of a Tertiary Care Center during the Second Wave.

Indian J Crit Care Med 2021 Oct;25(10):1193-1196

Department of Otorhinolaryngology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Rhino-orbital-cerebral mucormycosis is an invasive fungal infection associated with mortality of 25-62%. There has been a surge in the number of cases during this second wave of coronavirus disease-2019 (COVID-19) in India. We report 10 cases of mucormycosis admitted to our adult intensive care unit. After reviewing the patient's information, we found that 60% of patients had received steroids, and most had uncontrolled blood sugar levels. Most patients received treatment with surgical debridement and antifungal, although the mortality rate was as high as 40%. We report two unique cases of renal and gastrointestinal mucormycosis as well. We concluded that poor glycemic control was the primary etiology behind the rise in the number of cases. Our report also stresses the importance of early surgical intervention and suggests further research comparing the efficacy of combination antifungal therapy versus single antifungal (amphotericin B) to help resource-limited settings in these times of drug crisis. Yadav S, Sharma A, Kothari N, Bhatia PK, Goyal S, Goyal A. Mucormycosis: A Case Series of Patients Admitted in Non-COVID-19 Intensive Care Unit of a Tertiary Care Center during the Second Wave. Indian J Crit Care Med 2021;25(10):1193-1196.
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http://dx.doi.org/10.5005/jp-journals-10071-23986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645818PMC
October 2021

Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures.

Genome Med 2021 Dec 16;13(1):189. Epub 2021 Dec 16.

Genome Institute of Singapore, A*STAR, Singapore, Singapore.

While understanding molecular heterogeneity across patients underpins precision oncology, there is increasing appreciation for taking intra-tumor heterogeneity into account. Based on large-scale analysis of cancer omics datasets, we highlight the importance of intra-tumor transcriptomic heterogeneity (ITTH) for predicting clinical outcomes. Leveraging single-cell RNA-seq (scRNA-seq) with a recommender system (CaDRReS-Sc), we show that heterogeneous gene-expression signatures can predict drug response with high accuracy (80%). Using patient-proximal cell lines, we established the validity of CaDRReS-Sc's monotherapy (Pearson r>0.6) and combinatorial predictions targeting clone-specific vulnerabilities (>10% improvement). Applying CaDRReS-Sc to rapidly expanding scRNA-seq compendiums can serve as in silico screen to accelerate drug-repurposing studies. Availability: https://github.com/CSB5/CaDRReS-Sc .
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http://dx.doi.org/10.1186/s13073-021-01000-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8680165PMC
December 2021

A Composite Study of Coagulation Milieu in Covid-19: Experience from a Tertiary Care Centre from India.

Cardiovasc Hematol Disord Drug Targets 2021 ;21(3):185-195

All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Background: The understanding of pathogenesis is necessary for the development of effective treatment for COVID-19. Various studies have postulated that there is a complex interplay of mediators of coagulation and inflammation responsible for the pathogenesis of COVID-19. We did this study on coagulation parameters and inflammatory markers and their effect on outcome in patients with COVID-19.

Methods: This was a single centre observational cross-sectional study. Procoagulants [Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, lupus anticoagulant (LA), fibrinogen, factor-VIII (F-VIII)]; anticoagulants [protein-C (PC), protein-S (PS), antithrombin] and inflammatory markers [interleukin-6 (IL-6) and highly sensitive - C-reactive protein (hs-CRP)] were measured at the time of hospitalization and correlated with the severity of the disease.

Results: A total of 230 patients were enrolled, of which 61.3%, 20.0%, and 18.7% had asymptomatic/ mild, moderate, or severe disease, respectively. COVID-19 disease severity was associated with rising trends with coagulation parameters (PT, APTT, D-Dimer; p value 0.01, <0.0001, <0.0001, respectively). Falling trends of anticoagulant (PC, Antithrombin; p value <0.0001, 0.003 respectively) and rising trends of procoagulant (fibrinogen, F-VIII; p value 0.004, <0.0001 respectively) were observed with increasing COVID-19 disease severity. Multivariate logistic regression analysis found that advanced age, high D-Dimer, and high hs-CRP (p value 0.035, 0.018, <0.0001 respectively) were independent predictors of mortality in COVID-19. Procoagulant parameters (D-dimer, APTT, Factor VIII) were positively correlated with anticoagulant parameters (PC and PS) and inflammatory parameters (hs-CRP).

Conclusion: This study revealed increased levels of coagulation and inflammatory parameters, which correlated with the severity of COVID-19. Age, D-dimer, IL-6, hs-CRP, APTT, fibrinogen, and Factor VIII were significantly higher in patients with moderate and severe disease as compared to asymptomatic/mild disease. Advanced age, high D-dimer, and high hs-CRP were significantly associated with poor outcomes.
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http://dx.doi.org/10.2174/1871529X21666211201110007DOI Listing
January 2022

Ulcer due to prolonged use of high-flow nasal oxygen.

Braz J Anesthesiol 2021 Nov 27. Epub 2021 Nov 27.

All India Institute of Medical Sciences (AIIMS), Department of Anesthesia and Critical, Rajasthan, India.

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http://dx.doi.org/10.1016/j.bjane.2021.11.008DOI Listing
November 2021

TLR-Mediated Signal Transduction and Neurodegenerative Disorders.

Brain Sci 2021 Oct 20;11(11). Epub 2021 Oct 20.

Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida 201310, India.

A special class of proteins called Toll-like receptors (TLRs) are an essential part of the innate immune system, connecting it to the adaptive immune system. There are 10 different Toll-Like Receptors that have been identified in human beings. TLRs are part of the central nervous system (CNS), showing that the CNS is capable of the immune response, breaking the long-held belief of the brain's "immune privilege" owing to the blood-brain barrier (BBB). These Toll-Like Receptors are present not just on the resident macrophages of the central nervous system but are also expressed by the neurons to allow them for the production of proinflammatory agents such as interferons, cytokines, and chemokines; the activation and recruitment of glial cells; and their participation in neuronal cell death by apoptosis. This study is focused on the potential roles of various TLRs in various neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD), namely TLR2, TLR3, TLR4, TLR7, and TLR9 in AD and PD in human beings and a mouse model.
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http://dx.doi.org/10.3390/brainsci11111373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615980PMC
October 2021

Clinical features and mortality in COVID-19 SARI versus non COVID-19 SARI cases from Western Rajasthan, India.

J Family Med Prim Care 2021 Sep 30;10(9):3240-3246. Epub 2021 Sep 30.

Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, India.

Background: In March 2020, the Indian Council of Medical Research (ICMR) issued guidelines that all patients presenting with severe acute respiratory infections (SARI) should be investigated for coronavirus disease 2019 (COVID-19). Following the same protocol, in our institute, all patients with SARI were transferred to the COVID-19 suspect intensive care unit (ICU) and investigated for COVID-19.

Methods: This study was planned to examine the demographical, clinical features, and outcomes of the first 500 suspected patients of COVID-19 with SARI admitted in the COVID-19 suspect ICU at a tertiary care center. Between March 7 and July 20, 2020, 500 patients were admitted to the COVID-19 suspect ICU. We analyzed the demographical, clinical features, and outcomes between COVID-19 positive and negative SARI cases. The records of all the patients were reviewed until July 31, 2020.

Results: Of the 500 suspected patients admitted to the hospital, 88 patients showed positive results for COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) of the nasopharyngeal swabs. The mean age in the positive group was higher (55.31 ± 16.16 years) than in the negative group (40.46 ± 17.49 years) ( < 0.001). Forty-seven (53.4%) of these patients in the COVID-19 positive group and 217 (52.7%) from the negative group suffered from previously known comorbidities. The common symptoms included fever, cough, sore throat, and dyspnea. Eighty-five (20.6%) patients died in the COVID-19 negative group, and 30 (34.1%) died in the COVID-19 positive group ( = 0.006). Deaths among the COVID-19 positive group had a significantly higher age than deaths in the COVID-19 negative group ( < 0.001). Among the patients who died with positive COVID-19 status had substantially higher neutrophilia and lymphopenia ( < 0.001). X-ray chest abnormalities were almost three times more likely in COVID-19 deaths ( < 0.001).

Conclusion: In the present article, 17.6% of SARI were due to COVID-19 infection with significantly higher mortality (34.1%) in COVID-19 positive patients with SARI. Although all patients presenting as SARI have considerable mortality rates, the COVID-19-associated SARI cases thus had an almost one-third risk of mortality.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_14_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565113PMC
September 2021

Microfluidic Platforms to Unravel Mysteries of Alzheimer's Disease: How Far Have We Come?

Life (Basel) 2021 Sep 28;11(10). Epub 2021 Sep 28.

Department of Biotechnology, School of Engineering and Technology (SET), Sharda University, Greater Noida 201310, Uttar Pradesh, India.

Alzheimer's disease (AD) is a significant health concern with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells such as microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms.
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http://dx.doi.org/10.3390/life11101022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537508PMC
September 2021

Periodontal health of the geriatric population in old-age homes of Delhi, India.

J Indian Soc Periodontol 2021 Sep-Oct;25(5):427-431. Epub 2021 Aug 30.

Department of Public Health Dentistry, Faculty of Dental Sciences, SGT University, Gurgaon, Haryana, India.

Background: Periodontal disease is one of the leading causes of tooth loss in the geriatric population. Assessment of periodontal disease in a population is an important step in planning effective prevention and control programs for periodontal disease. Therefore, a study was carried out in old-age homes of Delhi to assess the periodontal status of 65-74-year-old elderly and recommend interventions to improve their periodontal health.

Materials And Methods: A cross-sectional study was conducted among 464 elderly from old-age homes of Delhi. Periodontal health status of the participants was determined using the WHO oral health assessment form. Community Periodontal Index (CPI) and loss of attachment (LOA) were recorded. Collected data were analyzed using SPSS version 23. Chi-square test was used to determine statistically significant difference among CPI scores and LOA according to age and gender. P ≤ 0.05 was considered statistically significant.

Results: The result of the study showed that 25.4% of the elderly had healthy periodontium, 71.1% had a periodontal pocket of 6 mm or more, and 2.40% had a pocket depth of 4-5 mm. Around 36% had 6-8 mm LOA and 34.70% had 9-11 mm LOA. The difference between CPI scores among gender and age group was not significant ( = 0.20, = 0.096). However, the difference among gender for LOA was found significant ( = 0.014).

Conclusion: The results from this study show that periodontal health of elderly residing in old-age homes is very poor. The periodontal status of this population can be enhanced by special collaborative efforts from the government and various nongovernmental organizations toward preventive and curative periodontal health services.
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http://dx.doi.org/10.4103/jisp.jisp_193_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452175PMC
August 2021

Cascade of Complications Following Carotid Body Tumor Excision.

Neurointervention 2021 Nov 29;16(3):298-302. Epub 2021 Sep 29.

Department of Diagnostic and Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, India.

Carotid body tumor excision can lead to various complications including vascular injury and pseudoaneurysm formation. Here we describe a case of carotid body tumor excision followed by series of complications including pseudoaneurysm formation, failure of primary surgical repair, carotid stump syndrome following parent artery occlusion, and persistent hypotension.
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http://dx.doi.org/10.5469/neuroint.2021.00248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561026PMC
November 2021

Role of melatonin in attenuation of hemodynamic response to intubation and anesthetic requirements: a randomized, controlled, double-blind study.

Braz J Anesthesiol 2021 Sep 21. Epub 2021 Sep 21.

Dr. S.N. Medical College, Department of Orthopedics, Jodhpur, India.

Background: Melatonin has been studied to have anxiolytic, sedative, and analgesic effects. However, there is limited data on the effect of melatonin in the attenuation of hemodynamic response to intubation. We aimed to study whether preanesthetic oral melatonin attenuates hemodynamic responses to intubation and anesthetic requirements.

Methods: Sixty-four patients scheduled for laparoscopic cholecystectomy were randomized into melatonin or placebo group (n = 32 each). Melatonin group received two tablets (3 mg each) of melatonin, and the placebo group received two tablets of vitamin D3 120 min before induction. Hemodynamic parameters were recorded during induction and postintubation for 15 minutes. Total induction dose of propofol, total intraoperative fentanyl consumption, and adverse effects of melatonin were also noted.

Results: Postintubation rise in heart rate (HR) was less in the melatonin group compared to the placebo group (10.59% vs. 37.08% at 1 min, respectively) (p < 0.0001). Maximum percentage increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was lesser in melatonin group than placebo group (SBP 9.25% vs. 37.73%, DBP 10.58% vs. 35.51%, MBP 9.99% vs. 36.45% at 1 min postintubation. respectively) (p < 0.0001). Induction dose of propofol (1.42 mg.kg vs. 2.01 mg.kg) and the number of patients requiring additional fentanyl intraoperatively (3 vs. 11) were also significantly reduced in the melatonin group.

Conclusion: Premedication with 6 mg of oral melatonin resulted in significant attenuation of postintubation rise in HR, SBP, DBP, and MBP. It also reduced the induction dose of propofol, total intraoperative fentanyl consumption without any adverse effects.
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http://dx.doi.org/10.1016/j.bjane.2021.08.011DOI Listing
September 2021

Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates.

bioRxiv 2021 Sep 15. Epub 2021 Sep 15.

Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen Modified Vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.
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http://dx.doi.org/10.1101/2021.09.15.460487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452095PMC
September 2021

Antimicrobial activity of synthetic antimicrobial peptides loaded in poly-Ɛ-caprolactone nanoparticles against mycobacteria and their functional synergy with rifampicin.

Int J Pharm 2021 Oct 14;608:121097. Epub 2021 Sep 14.

Experimental Animal Facility, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India. Electronic address:

Tuberculosis (TB) treatment has become a challenge because of the natural presence of multilayered cell wall rich in lipids which restrict antibiotic permeability within the bacteria. The development of mutations conferring resistance has aggravated the situation. Consequently, maximum pharmaceutical efforts are required to improve the treatment, and antimicrobial peptides (AMPs) with antimycobacterial activity can be exploited as a new treatment strategy against TB. The synergistic interaction between conventional antibiotics and AMPs has broadened its application landscape. To overcome peptide instability and bioavailability issues, encapsulation of these bioactive in biocompatible polymers was adopted. In this study, the effect of synthetic AMPs HHC-8 [KIWWWWRKR] and MM-10 [MLLKKLLKKM] encapsulated in poly (ε-caprolactone) nanoparticles (PCL-NPs) was evaluated against mycobacteria using REMA (Resazurin Microtiter Assay Plate) technique. PCL encapsulation allowed us to load the required amount of peptides, i.e. HHC-8 and MM-10, with an efficiency of ∼ 18.9 ± 5.24 and ∼ 21.1 ± 6.19 % respectively, and sphere size was around 376.5 ± 14.9 nm and 289.87 ± 17.98 nm for PCL-HHC-8-NPs and PCL-MM-10-NPs, respectively. Minimal degradation and sustained release of peptides from nanoparticles improved antimicrobial activity, decreasing the MIC from 75 µg/ml to 18.75 µg/ml against M. smegmatis and from 75 µg/ml to 9 µg/ml against M. tuberculosis, respectively. The combinatorial MIC assays of encapsulated AMP with rifampicin antibiotics against M. smegmatis showed synergism between AMP-PCL-NPs and antibiotics with fractional inhibitory concentrations (FICs) around ∼ 0.09. The combinations of AMP NPs also demonstrated synergy against the mycobacteria. Our findings suggest that enhanced efficacy is due to protection offered by AMPs encapsulation resulting in augmentation of membrane permeation by AMPs and enhanced accumulation of antibiotics within mycobacteria resulting in synergy. The study findings might assist in the preclinical development of AMP for the fight against TB.
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http://dx.doi.org/10.1016/j.ijpharm.2021.121097DOI Listing
October 2021

Clinical profile of bloodstream infections in COVID-19 patients: a retrospective cohort study.

BMC Infect Dis 2021 Sep 8;21(1):933. Epub 2021 Sep 8.

All India Institute of Medical Sciences, Jodhpur, 342005, India.

Background: Bloodstream infections (BSIs) are an emerging cause of significant morbidity and mortality in severe Coronavirus disease 2019 (COVID-19). We aimed to assess the prevalence, clinical profile and outcome of BSIs in critically ill COVID-19 patients.

Methods: This was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age > 18 years) with reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 admitted in the intensive care unit (ICU) were included. Hospital electronic records were searched for demographic data, time of bloodstream infection since admission, clinical profile, antimicrobial resistance pattern and clinical outcome of all patients who developed BSIs.

Results: Out of 750 patients admitted in COVID ICU, 8.5% developed secondary BSIs. All severe COVID-19 patients who developed BSIs succumbed to illness. A significant proportion of BSIs were Gram-negative pathogens (53/64, 82.8%). Acinetobacter baumannii was the commonest isolate, followed by Klebsiella pneumoniae (32.8% and 21.9%, respectively). Multidrug-resistance organisms (MDRO) were found in 57.8% of the cases. The majority of MDRO belonged to K. pneumoniae and Enterococcus groups. The proportion of Gram-negative bacteria resistant to carbapenems was 47.2% (25/53). On multivariate analysis, raised total leukocyte counts, mechanical ventilation and presence of comorbidities were significantly associated with the incidence of BSIs.

Conclusion: We found a significant prevalence of Acinetobacter baumannii in COVID-19 associated BSIs. The presence of comorbidities raised leukocyte counts and mechanical ventilation should alarm clinicians for possible BSIs. The timely initiation of empirical antibiotics and rapid de-escalation is vital to improve the outcome. At the same time, strict compliance of infection control practices should be accomplished to reduce the occurrence of MDRO.
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http://dx.doi.org/10.1186/s12879-021-06647-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424166PMC
September 2021

A subset of Kupffer cells regulates metabolism through the expression of CD36.

Immunity 2021 09 31;54(9):2101-2116.e6. Epub 2021 Aug 31.

Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.

Tissue macrophages are immune cells whose phenotypes and functions are dictated by origin and niches. However, tissues are complex environments, and macrophage heterogeneity within the same organ has been overlooked so far. Here, we used high-dimensional approaches to characterize macrophage populations in the murine liver. We identified two distinct populations among embryonically derived Kupffer cells (KCs) sharing a core signature while differentially expressing numerous genes and proteins: a major CD206ESAM population (KC1) and a minor CD206ESAM population (KC2). KC2 expressed genes involved in metabolic processes, including fatty acid metabolism both in steady-state and in diet-induced obesity and hepatic steatosis. Functional characterization by depletion of KC2 or targeted silencing of the fatty acid transporter Cd36 highlighted a crucial contribution of KC2 in the liver oxidative stress associated with obesity. In summary, our study reveals that KCs are more heterogeneous than anticipated, notably describing a subpopulation wired with metabolic functions.
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http://dx.doi.org/10.1016/j.immuni.2021.08.006DOI Listing
September 2021

Editorial: Non-Genetic Heterogeneity in Development and Disease.

Front Genet 2021 9;12:731814. Epub 2021 Aug 9.

QEII Medical Centre and Centre for Medical Research, Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.

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http://dx.doi.org/10.3389/fgene.2021.731814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381376PMC
August 2021

Advances in pulmonary drug delivery targeting microbial biofilms in respiratory diseases.

Nanomedicine (Lond) 2021 09 5;16(21):1905-1923. Epub 2021 Aug 5.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW, 2007, Australia.

The increasing burden of respiratory diseases caused by microbial infections poses an immense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.
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http://dx.doi.org/10.2217/nnm-2021-0057DOI Listing
September 2021

Production of Transgenic Handmade Cloned Goat () Embryos by Targeted Integration into Rosa 26 Locus Using Transcription Activator-like Effector Nucleases.

Cell Reprogram 2021 08 4;23(4):250-262. Epub 2021 Aug 4.

Embryo Biotechnology Laboratory, Animal Biotechnology Centre, ICAR-National Dairy Research Institute, Karnal, India.

Transgenic goats are ideal bioreactors for the production of therapeutic proteins in their mammary glands. However, random integration of the transgene within-host genome often culminates in unstable expression and unpredictable phenotypes. Targeting desired genes to a safe locus in the goat genome using advanced targeted genome-editing tools, such as transcription activator-like effector nucleases (TALENs) might assist in overcoming these hurdles. We identified Rosa 26 locus, a safe harbor for transgene integration, on chromosome 22 in the goat genome for the first time. We further demonstrate that TALEN-mediated targeting of GFP gene cassette at Rosa 26 locus exhibited stable and ubiquitous expression of GFP gene in goat fetal fibroblasts (GFFs) and after that, transgenic cloned embryos generated by handmade cloning (HMC). The transfection of GFFs by the TALEN pair resulted in 13.30% indel frequency at the target site. Upon cotransfection with TALEN and donor vectors, four correctly targeted cell colonies were obtained and all of them showed monoallelic gene insertions. The blastocyst rate for transgenic cloned embryos (3.92% ± 1.12%) was significantly ( < 0.05) lower than cloned embryos (7.84% ± 0.68%) used as control. Concomitantly, 2 out of 15 embryos of morulae and blastocyst stage (13.30%) exhibited site-specific integration. In conclusion, the present study demonstrates TALEN-mediated transgene integration at Rosa 26 locus in caprine fetal fibroblasts and the generation of transgenic cloned embryos using HMC.
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http://dx.doi.org/10.1089/cell.2021.0011DOI Listing
August 2021

Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease.

Immunity 2021 08 30;54(8):1883-1900.e5. Epub 2021 Jul 30.

Gustave Roussy Cancer Campus, Villejuif, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1CD274(PD-L1)IDO1 macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.
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http://dx.doi.org/10.1016/j.immuni.2021.07.007DOI Listing
August 2021

30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.

Obes Surg 2021 10 30;31(10):4272-4288. Epub 2021 Jul 30.

Bariatric Unit, South Tyneside and Sunderland NHS Trust, Sunderland, UK.

Background: There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates.

Methods: We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020.

Results: Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country.

Conclusions: BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak.
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http://dx.doi.org/10.1007/s11695-021-05493-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323543PMC
October 2021

Effects of curcumin-loaded poly(lactic-co-glycolic acid) nanoparticles in MDA-MB231 human breast cancer cells.

Nanomedicine (Lond) 2021 08 23;16(20):1763-1773. Epub 2021 Jul 23.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia.

This study was aimed at evaluating the anticancer potential of curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) in MDA-MB231 human breast cancer cells. Curcumin-loaded PLGA NPs were developed using a modified solvent evaporation technique. Physical characterization was performed on the formulated NPs. Furthermore, experiments were conducted to study the biological activity of the curcumin-loaded NPs. Curcumin-loaded PLGA NPs demonstrated high encapsulation efficiency and sustained payload release. Moreover, the NPs exhibited a significant reduction in cell viability, cell migration and cell invasion in the MDA-MB231 cells. The study revealed that the formulated curcumin-loaded PLGA NPs possessed significant anti-metastatic properties. The findings showcased the possible potential of curcumin-loaded NPs in the management of debilitating conditions such as cancer. In addition, this study could form the basis for further research and advancements in this area.
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http://dx.doi.org/10.2217/nnm-2021-0066DOI Listing
August 2021

The Effect of Intermittent Preventive Treatment of Malaria During Pregnancy and Placental Malaria on Infant Risk of Malaria.

J Infect Dis 2022 01;225(2):248-256

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Background: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) provides greater protection from placental malaria than sulfadoxine-pyrimethamine (SP). Some studies suggest placental malaria alters risk of malaria infection in infants, but few have quantified the effect of IPTp on infant susceptibility to malaria.

Methods: Infants born to women enrolled in a randomized clinical trial comparing IPTp-SP and IPTp-DP in Malawi were followed from birth to 24 months to assess effect of IPTp and placental malaria on time to first malaria episode and Plasmodium falciparum incidence.

Results: In total, 192 infants born to mothers randomized to IPTp-SP and 195 randomized to IPTp-DP were enrolled. Infants in IPTp exposure groups did not differ significantly regarding incidence of clinical malaria (incidence rate ratio [IRR], 1.03; 95% confidence interval [CI], .58-1.86) or incidence of infection (IRR, 1.18; 95% CI, .92-1.55). Placental malaria exposure was not associated with incidence of clinical malaria (IRR, 1.03; 95% CI, .66-1.59) or infection (IRR, 1.15; 95% CI, .88-1.50). Infant sex, season of birth, and maternal gravidity did not confound results.

Conclusions: We did not find evidence that IPTp regimen or placental malaria exposure influenced risk of malaria during infancy in this population. Clinical Trials Registration. NCT03009526.
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http://dx.doi.org/10.1093/infdis/jiab351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763957PMC
January 2022

Perceptions of a university's faculty members on organ donation.

Natl Med J India 2020 Sep-Oct;33(5):302-305

Department of Public Health Dentistry, Manav Rachna Dental College and Hospital, Faridabad, Haryana, India.

Background: . Availability of donated organs may save lives of people with end-stage disease. However, multiple barriers exist for obtaining donated organs such as insufficient knowledge and lack of a positive attitude towards organ donation. We assessed the knowledge and attitude regarding organ donation among faculty members of a university in India.

Methods: . We did this observational, cross-sectional study from December 2017 to January 2018. A structured, close-ended questionnaire consisting of 20 items was used to assess knowledge, attitude and practices regarding organ donation. Data for 170 participants were analysed using SPSS version 21. Unpaired t-test was used to compare the knowledge and attitude score among different variables.

Results: . A statistically significant difference was found between the attitude score of graduate and postgraduate faculty (p=0.003), as well as between graduate and doctoral faculty (p=0.001). We found that 5.3% of participants had already donated organs, 12.9% had pledged to donate and 63.5% of participants had expressed willingness to donate organs.

Conclusions: . There is a need to increase the knowledge regarding organ donation as most people have a good attitude towards organ donation, but their knowledge was insufficient and at times inaccurate.
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http://dx.doi.org/10.4103/0970-258X.317462DOI Listing
October 2021

Sperm phenotypic characteristics and oviduct binding ability are altered in breeding bulls with high sperm DNA fragmentation index.

Theriogenology 2021 Sep 9;172:80-87. Epub 2021 Jun 9.

Dairy Production Section, Southern Regional Station of ICAR-National Dairy Research Institute, Bengaluru, 560030, Karnataka, India.

In the present study, we standardized an in vitro oviduct explants model for cattle and assessed the oviduct explants binding ability and phenotypic characteristics of spermatozoa obtained from breeding bulls with high- and low-sperm DNA fragmentation index (DFI%). Cryopreserved spermatozoa from Holstein Friesian crossbred breeding bulls (n = 45) with known field fertility were assessed for DFI% and were classified into either high DFI% or low DFI% category. Flow cytometry was used to assess sperm membrane integrity, acrosome reaction status, mitochondrial membrane potential and intracellular calcium concentrations. It was found that spermatozoa from bulls with low DFI% had significantly higher (P < 0.05) membrane integrity, acrosome intactness, and mitochondrial membrane potential. To assess the sperm oviduct binding ability, oviduct explants were prepared by incubating the oviduct cells overnight in TCM-199 medium at 38.5 °C under 5% CO. Different sperm concentrations and times of incubation were evaluated and found that 2 million spermatozoa and 1-h incubation yielded high binding index (BI). The BI was also significantly (P < 0.01) higher (>2 times) in the bulls with low-DFI% as compared to high DFI% bulls. The correlation between binding index and DFI% was negative and significant (r = -0.528; P < 0.05). Further, the binding index was positively correlated with conception rate (r = 0.703), intact sperm membrane (r = 0.631) and mitochondrial membrane potential (r = 0.609). It is inferred that sperm phenotypic characteristics and oviduct binding ability are impaired in breeding bulls with high sperm DFI%, which might be associated with low conception rates in these bulls.
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http://dx.doi.org/10.1016/j.theriogenology.2021.06.006DOI Listing
September 2021

Middle East Respiratory Syndrome (MERS) Virus-Pathophysiological Axis and the Current Treatment Strategies.

AAPS PharmSciTech 2021 Jun 8;22(5):173. Epub 2021 Jun 8.

Department of Life Sciences, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
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http://dx.doi.org/10.1208/s12249-021-02062-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186825PMC
June 2021

FDA approved ready to use phenylephrine.

J Anaesthesiol Clin Pharmacol 2021 Jan-Mar;37(1):141. Epub 2021 Apr 10.

Department of Trauma and Emergency (Anaesthesia) All India Institute of Medical Sciences, Jodhpur, Rajasthan India.

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http://dx.doi.org/10.4103/joacp.JOACP_379_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174445PMC
April 2021
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