Publications by authors named "S Khurana"

798 Publications

Latent Upregulation of and Differentiates between Asymptomatic and Symptomatic Infection.

Immunol Invest 2021 Apr 19:1-22. Epub 2021 Apr 19.

Dr. B. R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, Delhi, India.

is a parasitic protozoan that causes trichomoniasis. The involvement of NLRP3 inflammasome in trichomoniasis has been discussed in recent studies. The present study aimed to find out the involvement of , and in the BALB/c mouse model infected with symptomatic and asymptomatic isolates of by quantitative real-time PCR and immunohistochemistry. Our results showed a significantly increased expression of in the vaginal tissue of the symptomatic group on the 2 dpi and 14 dpi in the asymptomatic group, respectively. The cervical tissue of asymptomatic groups expressed higher on 14 dpi than the symptomatic group. The was expressed on 14 dpi in the vaginal and cervical tissues of mice infected with asymptomatic group as compared to the symptomatic group. expression in vaginal tissue was highest at early time points in both the infected groups as compared to controls. However, in cervical tissues, a significant increase of expression was observed on 14 dpi in asymptomatic as compared to the symptomatic group. The significantly higher expression of and was observed in cervical tissues of the asymptomatic group on 14 dpi as compared to the symptomatic group, respectively. All NLRs together resulted in higher IL-1β expression in the vaginal tissues of the symptomatic and asymptomatic groups. We conclude from this study that early expression of , and was seen in the symptomatic group as compared to the late-onset asymptomatic in the vaginal and cervical tissues.
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http://dx.doi.org/10.1080/08820139.2021.1909062DOI Listing
April 2021

Impact of convalescent plasma therapy on SARS CoV-2 antibody profile in COVID-19 patients.

Clin Infect Dis 2021 Apr 16. Epub 2021 Apr 16.

Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, Maryland, USA.

Convalescent plasma (CP) have been used for treatment of COVID-19, but their effectiveness varies significantly. Moreover, the impact of CP treatment on the composition of SARS-CoV-2 antibodies in COVID-19 patients and antibody markers that differentiate between those who survive and those who succumb to the COVID-19 disease are not well understood. Herein, we performed longitudinal analysis of antibody profile on 115 sequential plasma samples from 16 hospitalized COVID-19 patients treated with either CP or standard of care, only half of them survived. Differential antibody kinetics was observed for antibody binding, IgM/IgG/IgA distribution, and affinity maturation in 'survived' vs. 'fatal' COVID-19 patients. Surprisingly, CP treatment did not predict survival. Strikingly, marked decline in neutralization titers was observed in the fatal patients prior to death, and convalescent plasma treatment did not reverse this trend. Furthermore, irrespective of CP treatment, higher antibody affinity to the SARS-CoV-2 prefusion spike was associated with survival outcome, while sustained elevated IgA response was associated with fatal outcome in these COVID-19 patients. These findings propose that treatment of COVID-19 patients with convalescent plasma should be carefully targeted, and effectiveness of treatment may depend on the clinical and immunological status of COVID-19 patients as well as the quality of the antibodies in the convalescent plasma.
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http://dx.doi.org/10.1093/cid/ciab317DOI Listing
April 2021

Changes in extracellular cytokines in predicting disease severity and final clinical outcome of patients with blunt chest trauma.

Immunobiology 2021 Mar 27;226(3):152087. Epub 2021 Mar 27.

Division of Trauma Surgery & Critical Care, JPN Apex Trauma Center, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Background: Chest trauma causes substantial morbidity and mortality and its severity is assessed using clinical diagnosis or scoring systems like Injury severity score (ISS) and thoracic trauma severity score (TTSS). Association of inflammatory cytokines with severity of disease and final clinical outcome is not clearly defined in patients with chest trauma. In this study, we thought to evaluate the inflammatory response in serum and bronchoalveolar lavage fluid (BALF) in chest trauma patients and correlate the level of extracellular cytokines with diseases severity and final outcome.

Methods: A total of 65 patients with blunt chest trauma and 30 healthy controls were enrolled in this prospective observational study. Assessment of inflammatory cytokines such as Interleukin (s) - IL-5, IL-13, IL-2, IL-6, IL-9, IL-1β, IFN-γ, TNF-α, IL-17A, IL-17F,IL-4, IL-21 and IL-22 was performed in both serum and bronchoalveolar lavage fluid using 13-plex multiplex kit using fluorescence-encoded bead based immunoassays.

Results: A significantly higher level of IL-13, IL-2, IL-6, IL-9, IL-1β, IFN-γ, TNF-α, IL-17A, IL-17F, IL-21 and IL-22 cytokines were observed in patients with blunt chest trauma compared to healthy controls. Level of IL-2, IL-6, IL-1β and IL-17A was significantly raised in the patients with blunt chest trauma who had a fatal outcome during the hospital stay. An elevated cytokine response of IL-13, IL-4, and IL-21 was noted in the group of patients with high (>5) thoracic trauma severity score.

Conclusion: Routine monitoring of the inflammatory cytokine level in patients with chest trauma may be used routinely. Longer prospective studies should be encouraged to determine the role of cytokines in patients with chest trauma in predicting the patient final clinical outcome.
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http://dx.doi.org/10.1016/j.imbio.2021.152087DOI Listing
March 2021

Insights on and infection in poultry: a systematic review.

Anim Biotechnol 2021 Apr 10:1-10. Epub 2021 Apr 10.

ICAR-Central Institute for Research on Buffaloes, Hisar, India.

Avian mycoplasmosis mainly caused by and is an economically important disease of poultry industry. It causes huge economic losses in terms of decrease in weight gain, feed conversion efficiency, egg production, hatchability; increase in embryo mortality, carcass condemnation, prophylaxis and treatment cost in broiler, layer and breeder flocks. The disease is caused by four major pathogenic mycoplasmas ., (MG) (MS), (MM) and (MI). The MG and MS are World Organization for Animal Health listed respiratory pathogens. MG causes chronic respiratory disease in chicken and infectious sinusitis in turkey; however, MS causes synovitis and airsacculitis in birds. The infection is transmitted both horizontally and vertically. Prevention and control measures of avian mycoplasmosis mainly comprises of biosecurity, treatment and vaccination. For vaccination of birds, inactivated bacterins, live attenuated and/or recombinant live poxvirus vaccines are commercially available against MG and MS infection. The present systematic review summarizes the different epidemiological studies carried out on MG and MS infection in poultry in different geographical locations of India and abroad over the last decade (2010-2020), economic impact, diagnosis and prevention and control.
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http://dx.doi.org/10.1080/10495398.2021.1908316DOI Listing
April 2021

Rapid chromatographic immunoassay-based evaluation of COVID-19: A cross-sectional, diagnostic test accuracy study & its implications for COVID-19 management in India.

Indian J Med Res 2021 Jan & Feb;153(1 & 2):126-131

Department of Medicine, Pain Medicine & Critical Care, Centre, All India Institute of Medical Sciences, New Delhi, India.

Background & Objectives: Coronavirus disease 2019 (COVID-19) has so far affected over 41 million people globally. The limited supply of real-time reverse transcription-polymerase chain reaction (rRT-PCR) kits and reagents has made meeting the rising demand for increased testing incompetent, worldwide. A highly sensitive and specific antigen-based rapid diagnostic test (RDT) is the need of the hour. The objective of this study was to evaluate the performance of a rapid chromatographic immunoassay-based test (index test) compared with a clinical reference standard (rRT-PCR).

Methods: A cross-sectional, single-blinded study was conducted at a tertiary care teaching hospital in north India. Paired samples were taken for RDT and rRT-PCR (reference standard) from consecutive participants screened for COVID-19 to calculate the sensitivity and specificity of the RDT. Further subgroup analysis was done based on the duration of illness and cycle threshold values. Cohen's kappa coefficient was used to measure the level of agreement between the two tests.

Results: Of the 330 participants, 77 were rRT-PCR positive for SARS-CoV-2. Sixty four of these patients also tested positive for SARS-CoV-2 by RDT. The overall sensitivity and specificity were 81.8 and 99.6 per cent, respectively. The sensitivity of RDT was higher (85.9%) in participants with a duration of illness ≤5 days.

Interpretation & Conclusions: With an excellent specificity and moderate sensitivity, this RDT may be used to rule in COVID-19 in patients with a duration of illness ≤5 days. Large-scale testing based on this RDT across the country would result in quick detection, isolation and treatment of COVID-19 patients.
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http://dx.doi.org/10.4103/ijmr.IJMR_3305_20DOI Listing
April 2021

Oxidative Stress Mediates the Fetal Programming of Hypertension by Glucocorticoids.

Antioxidants (Basel) 2021 Mar 29;10(4). Epub 2021 Mar 29.

Biomolecular Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada.

The field of cardiovascular fetal programming has emphasized the importance of the uterine environment on postnatal cardiovascular health. Studies have linked increased fetal glucocorticoid exposure, either from exogenous sources (such as dexamethasone (Dex) injections), or from maternal stress, to the development of adult cardiovascular pathologies. Although the mechanisms are not fully understood, alterations in gene expression driven by altered oxidative stress and epigenetic pathways are implicated in glucocorticoid-mediated cardiovascular programming. Antioxidants, such as the naturally occurring polyphenol epigallocatechin gallate (EGCG), or the superoxide dismutase (SOD) 4-hydroxy-TEMPO (TEMPOL), have shown promise in the prevention of cardiovascular dysfunction and programming. This study investigated maternal antioxidant administration with EGCG or TEMPOL and their ability to attenuate the fetal programming of hypertension via Dex injections in WKY rats. Results from this study indicate that, while Dex-programming increased blood pressure in male and female adult offspring, administration of EGCG or TEMPOL via maternal drinking water attenuated Dex-programmed increases in blood pressure, as well as changes in adrenal mRNA and protein levels of catecholamine biosynthetic enzymes phenylalanine hydroxylase (), tyrosine hydroxylase (), dopamine beta hydroxylase (), and phenylethanolamine N-methyltransferase (), in a sex-specific manner. Furthermore, programmed male offspring displayed reduced antioxidant glutathione peroxidase 1 () expression, increased superoxide dismutase 1 () and catalase () expression, and increased pro-oxidant NADPH oxidase activator 1 (Noxa1) expression in the adrenal glands. In addition, prenatal Dex exposure alters expression of epigenetic regulators histone deacetylase () 1, 5, 6, 7, 11, in male and in female offspring. These results suggest that glucocorticoids may mediate the fetal programming of hypertension via alteration of epigenetic machinery and oxidative stress pathways.
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http://dx.doi.org/10.3390/antiox10040531DOI Listing
March 2021

A multi-stakeholder Delphi consensus core outcome set for clinical trials in moderate-to-severe asthma (coreASTHMA).

Ann Allergy Asthma Immunol 2021 Mar 26. Epub 2021 Mar 26.

Center for Medical Technology Policy, Baltimore, Maryland.

Background: Treatments for long-term control of asthma have improved and include a promising but expensive class of biologic therapies. However, the clinical trials evaluating these and other novel treatments have utilized a variety of different outcomes to evaluate efficacy. The evolution of asthma care calls for a re-examination of outcomes that are most important to patients and other stakeholders.

Objective: The coreASTHMA project sought to develop a core set of outcomes to be measured in phase 3 and phase 4 clinical drug trials in patients with moderate-to-severe asthma.

Methods: We utilized a robust and in-depth multi-stakeholder consensus process bringing together patients, clinicians, regulators, payers, health technology assessors, researchers, and product developers to reach consensus on outcomes. We employed a modified Delphi method to reach consensus, an approach adapted from the Core Outcome Measures in Effectiveness Trials Initiative aligned with contemporary methodological standards for core outcome set development.

Results: The following outcomes were included in the final core set: severe asthma exacerbation, change in asthma control, asthma-specific or severe asthma-specific quality of life, asthma-specific hospital stay (i.e. >24 hour stays at any level of care) or admission, and asthma-specific emergency department visit.

Conclusion: These five outcomes represent a minimum set of core outcomes for use in phase 3 and phase 4 clinical drug trials in moderate-to-severe asthma. Consistent collection of these outcomes as minimum, independent of whether additional heterogeneous primary or secondary outcomes are included, will allow for meaningful comparisons across clinical trials of the effect of asthma therapies.
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http://dx.doi.org/10.1016/j.anai.2021.03.022DOI Listing
March 2021

Industrially produced trans fat: Usage, health implications, global and indian regulations.

Indian J Public Health 2021 Jan-Mar;65(1):71-75

Lead Expert, Science and Standards Division, Food Safety and Standards Authority of India, Delhi, India.

Global momentum is growing for the total elimination of industrially produced trans fats from the food systems as they are known to have deleterious health effects on various body functions particularly the cardiovascular health. Many developed nations such as Denmark have completely eliminated the use of industrially produced trans fats from the food supply. India is undergoing a significant nutrition transition that has substantially increased the intake of processed and ready-to-eat foods, abundant in trans fats. The Indian regulator-Food Safety and Standards Authority of India is all set to reduce the industrially produced trans fats to <2% by the end of year 2021 in a phased manner. Multiple strategies such as reducing trans fat limit in oils and fats, mandatory labeling on food products, introduction of "Trans-fat free" claim and logo have been adopted by the Indian regulatory body, to achieve the goal of trans fat free India. This review comprehensively summarizes from a public health perspective the usage of industrially-produced trans fats in Indian food industry, its effects on health, the global strategies to limit its content, and the current Indian regulations.
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http://dx.doi.org/10.4103/ijph.IJPH_851_20DOI Listing
March 2021

Pondicherry declaration on the identification and detection of .

Trop Parasitol 2020 Jul-Dec;10(2):71-73. Epub 2021 Jan 25.

Department of Microbiology, Mahatma Gandhi Medical College and Research Institute, Puducherry, India.

Stake holders meet on "Identification and Detection of " was conducted on July 21, 2019 at Sri Balaji Vidyapeeth Deemed-to-be-University, Pondicherry. This programme was of national importance, since the amoebiasis is being increasingly reported from different parts of India because of poor socioeconomic conditions and sanitation levels. Experts in amoebiasis research across India attended this meeting. This meeting was conducted with an objective to frame the guidelines on the identification and detection of with reference to conventional diagnostic methods and molecular diagnosis targeting appropriate genes of . The recommendations of the panel were released as declaration on the diagnosis of amoebiasis and were circulated to various administrative and scientific bodies in India as reference policy document on the diagnosis of amoebiasis.
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http://dx.doi.org/10.4103/tp.TP_111_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951082PMC
January 2021

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer.

Oncology 2021 Mar 18:1-8. Epub 2021 Mar 18.

Department of Medical Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India.

Background: Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin.

Methods: This open-label randomized trial was designed to compare pemetrexed-carboplatin with (weekly) paclitaxel-carboplatin in treatment-naïve advanced/metastatic non-squamous NSCLC without driver mutations. Patients received either pemetrexed 500 mg/m2 and carboplatin AUC 5 every 3 weeks, or paclitaxel 80 mg/m2 on day 1, day 8, and day 15 with carboplatin AUC 5 every 4 weeks for 4 cycles. Patients in both arms were allowed to receive pemetrexed maintenance.

Results: A total of 180 patients were enrolled. The study was terminated early; however, at the time of analysis 75.8% of the required events had occurred. Finally, 164 patients were evaluable, 83 in the pemetrexed arm and 81 in the paclitaxel arm. After a median follow-up of 17 months, progression-free survival (PFS) rates at 6 months were not different in the two treatment arms (47.45 vs. 48.64%, p = 0.88). The median PFS values were 5.67 months (95% CI 3.73-7.3) and 5.03 months (95% CI 2.63-7.43) in each arm, respectively (HR 1.13, 95% CI 0.81-1.59, p = 0.44). The median overall survival was also not different: 14.83 months (95% CI 9.5-18.73) and 11.3 (95% CI 8.3-19.7; HR 1.19, 95% CI 0.8-1.78, p = 0.37). All grade toxicities were similar except for alopecia and peripheral neuropathy, which were higher in the paclitaxel arm.

Conclusion: Pemetrexed-carboplatin is not superior to (weekly) paclitaxel-carboplatin as the first-line regimen in advanced non-squamous NSCLC in terms of PFS.
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http://dx.doi.org/10.1159/000514577DOI Listing
March 2021

Longitudinal antibody repertoire in "mild" versus "severe" COVID-19 patients reveals immune markers associated with disease severity and resolution.

Sci Adv 2021 03 5;7(10). Epub 2021 Mar 5.

Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20871, USA.

Limited knowledge exists on immune markers associated with disease severity or recovery in patients with coronavirus disease 2019 (COVID-19). Here, we elucidated longitudinal evolution of SARS-CoV-2 antibody repertoire in patients with acute COVID-19. Differential kinetics was observed for immunoglobulin M (IgM)/IgG/IgA epitope diversity, antibody binding, and affinity maturation in "severe" versus "mild" COVID-19 patients. IgG profile demonstrated immunodominant antigenic sequences encompassing fusion peptide and receptor binding domain (RBD) in patients with mild COVID-19 who recovered early compared with "fatal" COVID-19 patients. In patients with severe COVID-19, high-titer IgA were observed, primarily against RBD, especially in patients who succumbed to SARS-CoV-2 infection. The patients with mild COVID-19 showed marked increase in antibody affinity maturation to prefusion SARS-CoV-2 spike that associated with faster recovery from COVID-19. This study revealed antibody markers associated with disease severity and resolution of clinical disease that could inform development and evaluation of effective immune-based countermeasures against COVID-19.
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http://dx.doi.org/10.1126/sciadv.abf2467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935365PMC
March 2021

Persistent Human Papillomavirus Infection.

Viruses 2021 02 20;13(2). Epub 2021 Feb 20.

Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 209892, USA.

Persistent infection with oncogenic human papillomavirus (HPV) types is responsible for ~5% of human cancers. The HPV infectious cycle can sustain long-term infection in stratified epithelia because viral DNA is maintained as low copy number extrachromosomal plasmids in the dividing basal cells of a lesion, while progeny viral genomes are amplified to large numbers in differentiated superficial cells. The viral E1 and E2 proteins initiate viral DNA replication and maintain and partition viral genomes, in concert with the cellular replication machinery. Additionally, the E5, E6, and E7 proteins are required to evade host immune responses and to produce a cellular environment that supports viral DNA replication. An unfortunate consequence of the manipulation of cellular proliferation and differentiation is that cells become at high risk for carcinogenesis.
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http://dx.doi.org/10.3390/v13020321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923415PMC
February 2021

Recent advances in the treatment of infection: the ever-changing guidelines.

Fac Rev 2020 18;9:13. Epub 2020 Nov 18.

Associate Professor, Department of Gastroenterology, Hepatology and Nutrition, The University of Texas Health Science Center at Houston, Houston, TX, USA.

infection (CDI), formerly known as , continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.
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http://dx.doi.org/10.12703/b/9-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886080PMC
November 2020

Clinical and laboratory profile of trichinellosis from a non-endemic country.

Indian J Med Microbiol 2021 Feb 27. Epub 2021 Feb 27.

Department of Medical Parasitology, PGIMER, Chandigarh, India. Electronic address:

Trichinellosis is a zoonotic parasitic infection caused by nematodes of the genus Trichinella. Humans mostly get infected by eating raw/under-cooked pork. In India, it has been reported mostly as sporadic cases especially from North Eastern and Eastern part of country. In this study, we retrospectively analyzed the socio-demographic pattern, clinical presentation, laboratory profile and treatment response in Trichinella-infected patients visiting our tertiary care center which mainly caters to patients from North India. For this retrospective laboratory-based analysis, patients diagnosed on the basis of positive anti-Trichinella IgG antibodies between 1 June 2008, and 31 May 2019 were included. A total of 11 positive trichinellosis cases were detected, of whom majority were children who presented with history of fever, gastrointestinal symptoms, myalgia, eosinophilia along with hepatomegaly and pulmonary manifestations. No CNS involvement was seen in any of the patients although it is commonly associated with Trichinella infection. All patients recovered uneventfully after antihelminthic treatment.
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http://dx.doi.org/10.1016/j.ijmmb.2021.02.004DOI Listing
February 2021

Niche-Mediated Integrin Signaling Supports Steady-State Hematopoiesis in the Spleen.

J Immunol 2021 Apr 26;206(7):1549-1560. Epub 2021 Feb 26.

School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Kerala 695551, India;

Outside-in integrin signaling regulates cell fate decisions in a variety of cell types, including hematopoietic stem cells (HSCs). Our earlier published studies showed that interruption of periostin (POSTN) and integrin-αv (ITGAV) interaction induces faster proliferation in HSCs with developmental stage-dependent functional effects. In this study, we examined the role of POSTN-ITGAV axis in lymphohematopoietic activity in spleen that hosts a rare population of HSCs, the functional regulation of which is not clearly known. -mediated deletion of in the hematopoietic system led to higher proliferation rates, resulting in increased frequency of primitive HSCs in the adult spleen. However, in vitro CFU-C assays demonstrated a poorer differentiation potential following deletion. This also led to a decrease in the white pulp area with a significant decline in the B cell numbers. Systemic deletion of its ligand, POSTN, phenocopied the effects noted in mice. Histological examination of -deficient spleen also showed an increase in the spleen trabecular areas. Importantly, these are the myofibroblasts of the trabecular and capsular areas that expressed high levels of POSTN within the spleen tissue. In addition, vascular smooth muscle cells also expressed POSTN. Through CFU-S assays, we showed that hematopoietic support potential of stroma in -deficient splenic hematopoietic niche was defective. Overall, we demonstrate that POSTN-ITGAV interaction plays an important role in spleen lymphohematopoiesis.
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http://dx.doi.org/10.4049/jimmunol.2001066DOI Listing
April 2021

Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients.

Nat Commun 2021 02 22;12(1):1221. Epub 2021 Feb 22.

Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, USA.

Hospitalized COVID-19 patients often present with a large spectrum of clinical symptoms. There is a critical need to better understand the immune responses to SARS-CoV-2 that lead to either resolution or exacerbation of the clinical disease. Here, we examine longitudinal plasma samples from hospitalized COVID-19 patients with differential clinical outcome. We perform immune-repertoire analysis including cytokine, hACE2-receptor inhibition, neutralization titers, antibody epitope repertoire, antibody kinetics, antibody isotype and antibody affinity maturation against the SARS-CoV-2 prefusion spike protein. Fatal cases demonstrate high plasma levels of IL-6, IL-8, TNFα, and MCP-1, and sustained high percentage of IgA-binding antibodies to prefusion spike compared with non-ICU survivors. Disease resolution in non-ICU and ICU patients associates with antibody binding to the receptor binding motif and fusion peptide, and antibody affinity maturation to SARS-CoV-2 prefusion spike protein. Here, we provide insight into the immune parameters associated with clinical disease severity and disease-resolution outcome in hospitalized patients that could inform development of vaccine/therapeutics against COVID-19.
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http://dx.doi.org/10.1038/s41467-021-21463-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900119PMC
February 2021

Microbiological diagnosis of Acanthamoebic keratitis: experience from tertiary care center of North India.

Diagn Microbiol Infect Dis 2021 Feb 3;100(2):115339. Epub 2021 Feb 3.

Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

Acanthamoeba keratitis (AK) is a painful vision-threatening infection caused by pathogenic free-living Acanthamoeba. Due to the non-specific clinical presentation, this condition tends to be misdiagnosed by clinicians. A timely diagnosis is crucial for favorable visual outcome. Three hundred patients with suspected microbial keratitis presenting to the Advanced Eye Center at our tertiary care center in North India during the period from 2014 to 2018 were included. Patient's corneal scrapings, contact lens, lens solution, lens case, and tears were processed for microscopic examination by Giemsa and Calcofluor staining, non-nutrient agar (NNA) culture and molecular diagnosis by conventional PCR (cPCR) and Real-time PCR (qPCR). 18S rDNA gene sequencing was done to assess phylogenetic relationship. AK was found in 3.6% (11/300) of non-bacterial non-fungal keratitis patients. Among microbiological techniques, microscopy for Acanthamoeba was positive in 7 cases, NNA culture was positive in 9 cases and 11 cases were detected both by cPCR and qPCR. The sensitivity of microscopy, culture, cPCR and qPCR was 63.64%, 81.82 %, 100%, and 100% respectively whereas specificity was 100% for all the tests. 18S rDNA sequencing revealed that A. castellanii was the predominant species and isolates were genetically distinct. AK should be considered in the differential diagnosis of infectious keratitis. Molecular tests are useful for rapid, sensitive and specific diagnosis and must be included in workup of keratitis.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115339DOI Listing
February 2021

Device associated infections at a trauma surgical center of India: Trend over eight years.

Indian J Med Microbiol 2021 Jan 4;39(1):15-18. Epub 2020 Nov 4.

Department of Orthopaedics, Chief, JPN Apex Trauma Center, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Background: Device-associated infections (DAIs) are an important cause of excessive stay and mortality in ICUs. Trauma patients are predisposed to acquire such infections due to various factors. The prevalence of HAIs is underreported from developing nations due to a lack of systematic surveillance. This study reports the rates and outcomes of DAIs at a dedicated Trauma Center in trauma patients and compares the rates with a previous pilot observation.

Methods: The study reports the finding of ongoing surveillance and the use of an indigenous software at a level-1 trauma center in India. Surveillance for ventilator-associated pneumonia, central line-associated bloodstream infections, and catheter-associated urinary tract infections was done based on standard definitions. The rates of HAIs and the profile of pathogens isolated from June 2010 to December 2018 were analyzed.

Results: A total of 7485 patients were included in the analysis, amounting to 68,715 patient days. The rates of VAP, CLABSI, and CA-UTI were respectively 12, 9.8 1st 8.5/1000 device days. There was a significant correlation between device days and the propensity to develop infections. Of the 1449 isolates recovered from cases of DAIs, Acinetobacter sp (28.2%) was the most common isolate, followed by Candida sp. A high rate of multi-resistance was observed.

Conclusion: Automated surveillance was easy and useful for data entry and analysis. Surveillance data should be used for implementing preventive programs.
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http://dx.doi.org/10.1016/j.ijmmb.2020.10.015DOI Listing
January 2021

Differences in patient perceptions of integrated care among black, hispanic, and white Medicare beneficiaries.

Health Serv Res 2021 Feb 11. Epub 2021 Feb 11.

Stanford University School of Medicine, Stanford, California, USA.

Objective: This study sought to identify potential disparities among racial/ethnic groups in patient perceptions of integrated care (PPIC) and to explore how methodological differences may influence measured disparities.

Data Source: Data from Medicare beneficiaries who completed the 2015 Medicare Current Beneficiary Survey (MCBS) and were enrolled in Part A benefits for an entire year.

Study Design: We used 4-point measures of eight dimensions of PPIC and assessed differences in dimensions among racial/ethnic groups. To estimate differences, we applied a "rank and replace" method using multiple regression models in three steps, balancing differences in health status among racial groups and adjusting for differences in socioeconomic status. We reran all analyses with additional SES controls and using standard multiple variable regression.

Data Collection/extraction Methods: Not applicable.

Principal Findings: We found several significant differences in perceived integrated care between Black versus White (three of eight measures) and Hispanic versus White (one of eight) Medicare beneficiaries. On average, Black beneficiaries perceived more integrated support for self-care than did White beneficiaries (mean difference = 0.14, SE = 0.06, P =.02). Black beneficiaries perceived more integrated specialists' knowledge of past medical history than did White beneficiaries (mean difference = 0.12, SE = 0.06, P =.01). Black and Hispanic beneficiaries also each reported, on average, 0.18 more integrated medication and home health management than did White beneficiaries (P <.01 and P <.01). These findings were robust to sensitivity analyses and model specifications.

Conclusions: There exist some aspects of care for which Black and Hispanic beneficiaries may perceive greater integrated care than non-Hispanic White beneficiaries. Further studies should test theories explaining why racial/ethnic groups perceive differences in integrated care.
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http://dx.doi.org/10.1111/1475-6773.13637DOI Listing
February 2021

Surface Nanohardness of Normal and Fluorosed Enamel Adjacent to Restorative Materials: An Study and Polarized Light Microscopy Analysis.

J Contemp Dent Pract 2020 Sep 1;21(9):1034-1041. Epub 2020 Sep 1.

Department of Oral Pathology, JSS Dental College and Hospital, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India.

Aim And Objective: To evaluate nanohardness of normal and fluorosed enamel in teeth restored with Cention N (CN), Equia forte (EF), glass ionomer cement (GIC), and resin composite using the nanoindentation test.

Materials And Methods: Eighty freshly extracted human premolars were selected. Standardized cavities were prepared on the buccal surface of normal (40) and fluorosed (40) teeth. Based on the type of the restorative material, the teeth were subgrouped into ( = 10): CN, EF, Type VIII GIC, and Tetric N-Ceram (TNC). The teeth were subjected to pH cycle (progressive caries test), which consisted of alternative demineralization (18 hours) and remineralization with artificial saliva (6 hours) for 3 consecutive days. Surface nanohardness was determined using a nanoindenter at distances of 100, 200, and 300 μm from the restoration-tooth margin. A polarized light Microscope was used to correlate the effect of remineralization on the enamel. Data were analyzed by one-way ANOVA with the Scheffe's and independent -test.

Results: Nanohardness values of the fluorosed/normal enamel adjacent to various materials in descending order were as follows: EF 3.67/2.95 GPa, GIC 3.33/3.15 GPa, CN 3.13/3.23 GPa, and TNC 1.17/1.82 GPa, respectively. Statistically significant differences were found among various materials in both types of the enamel ( < 0.05).

Conclusion: Based on the nanohardness test, EF can be a better choice for restoration in fluorosed teeth, followed by CN and GIC; GIC was better in normal enamel; however, this was not significant compared to CN and EF. Tetric N-Ceram composite resin had least influence on increasing the nanohardness of the adjacent enamel.

Clinical Significance: The surface nanohardness of normal and fluorosed enamel can be influenced by the type of restorative material used. The results of present study deserve clinician's attention while selecting restorative materials especially in dental fluorosis.
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September 2020

A Comprehensive Review Evaluating the Impact of Protein Source (Vegetarian vs. Meat Based) in Hepatic Encephalopathy.

Nutrients 2021 Jan 26;13(2). Epub 2021 Jan 26.

Geisinger Medical Center, Department of Gastroenterology and Hepatology, Danville, PA 17822, USA.

Hepatic encephalopathy (HE) is a common neurological consequence in patients with cirrhosis and has a healthcare burden of USD 5370 to 50,120 per patient annually. HE significantly hampers the quality of life and is a major cause of morbidity and mortality. Patients with cirrhosis are at a high risk for protein-calorie malnutrition due to altered metabolism. Current evidence has changed the old belief of protein restriction in patients with cirrhosis and now 1.2 to 1.5 g/kg/day protein intake is recommended. Case series and studies with small numbers of participants showed that a vegetarian protein diet decreases the symptoms of HE when compared to a meat-based diet, but the evidence is limited and requires further larger randomized controlled trials. However, vegetable or milk-based protein diets are good substitutes for patients averse to meat intake. Branch chain amino acids (BCAA) (leucine, isoleucine and valine) have also been shown to be effective in alleviating symptoms of HE and are recommended as an alternative therapy in patients with cirrhosis for the treatment of HE. In this review, we provide an overview of current literature evaluating the role of protein intake in the management of HE in cirrhosis.
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http://dx.doi.org/10.3390/nu13020370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911290PMC
January 2021

Late gestational exposure to dexamethasone and fetal programming of abnormal behavior in Wistar Kyoto rats.

Brain Behav 2021 Apr 2;11(4):e02049. Epub 2021 Feb 2.

Biomolecular Sciences, Laurentian University, Sudbury, ON, Canada.

Introduction: Fetal programming was characterized a few decades ago, explaining the correlation of physiological phenotypes of offspring exposed to early-life stress. High acute or chronic prenatal stress can overwhelm the enzymatic placental barrier, inducing transcriptional changes in the fetus that can result in different adverse behavioral and physiological phenotypes. The current study investigates the impact of exposure to the synthetic glucocorticoid, dexamethasone, during late gestation on behavioral outcomes.

Methods: Pregnant Wistar Kyoto rats were given daily subcutaneous injections from gestational days 15-21 of either dexamethasone (0.9% NaCl, 4% EtOH, 100 µg kg  day ) or were physically manipulated as naïve controls. Pups were raised normally until 17 weeks of age and underwent the Porsolt swim task and elevated plus maze for depressive and anxiety-like behaviors, respectively. Neural tissue was preserved for genetic analysis using quantitative real-time polymerase chain reaction.

Results: Statistical analyses show significant disruption of behavior and genetic profiles of offspring exposed to dexamethasone in-utero. Exposed animals spent more time immobile on the swim task and entered open arms of the elevated plus maze more often than their naïve counterparts. In the prefrontal cortex, there was a sex by treatment interaction on gene expression relevant to neural transmission in ryanodine receptor 2, as well as increased gene expression in SNAP25, COMT, and LSAMP in males prenatally exposed to dexamethasone compared with controls. Both dysregulated genes and behavior are linked to decreased anxiety and fear inhibition.

Conclusion: Our results indicate adult offspring exposed to dexamethasone in-utero have a tendency toward passive stress-coping strategies and an inhibition of anxiety on behavioral tasks. Methyltransferase activity, synaptic activity, and cellular processes were disrupted in the prefrontal cortices of these animals. Specifically, genes involved in emotional response pathways were overexpressed, supporting the link between the behavioral and genetic profiles. Combined, we determine that dexamethasone offspring have adaptive predispositions when faced with novel situations, with increased immobility in the swim task and increased exploration on the elevated plus maze.
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http://dx.doi.org/10.1002/brb3.2049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035474PMC
April 2021

Advances in therapeutic and managemental approaches of bovine mastitis: a comprehensive review.

Vet Q 2021 Dec;41(1):107-136

Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Mastitis (intramammary inflammation) caused by infectious pathogens is still considered a devastating condition of dairy animals affecting animal welfare as well as economically incurring huge losses to the dairy industry by means of decreased production performance and increased culling rates. Bovine mastitis is the inflammation of the mammary glands/udder of bovines, caused by bacterial pathogens, in most cases. Routine diagnosis is based on clinical and subclinical forms of the disease. This underlines the significance of early and rapid identification/detection of etiological agents at the farm level, for which several diagnostic techniques have been developed. Therapeutic regimens such as antibiotics, immunotherapy, bacteriocins, bacteriophages, antimicrobial peptides, probiotics, stem cell therapy, native secretory factors, nutritional, dry cow and lactation therapy, genetic selection, herbs, and nanoparticle technology-based therapy have been evaluated for their efficacy in the treatment of mastitis. Even though several strategies have been developed over the years for the purpose of managing both clinical and subclinical forms of mastitis, all of them lacked the efficacy to eliminate the associated etiological agent when used as a monotherapy. Further, research has to be directed towards the development of new therapeutic agents/techniques that can both replace conventional techniques and also solve the problem of emerging antibiotic resistance. The objective of the present review is to describe the etiological agents, pathogenesis, and diagnosis in brief along with an extensive discussion on the advances in the treatment and management of mastitis, which would help safeguard the health of dairy animals.
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http://dx.doi.org/10.1080/01652176.2021.1882713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906113PMC
December 2021

Acanthamoeba keratitis in a mouse model using a novel approach.

Indian J Med Microbiol 2021 Jan 27. Epub 2021 Jan 27.

Department of Medical Parasitology, Post Graduate Institute of Medical Education &Research, Chandigarh, India. Electronic address:

Context: Acanthamoeba is increasingly implicated in causing keratitis in patients wearing contact lens or ocular trauma and has a poor prognosis. Establishment of an animal model is critical to study the disease pathology, pathogenesis and to evaluate anti-amoebic drugs. Some studies have used contact lenses to establish Acanthamoeba keratitis (AK) in a mouse model, which is expensive and not very successful as lenses get dislodged.

Objective: To assess the feasibility of using parafilm (Bemis Company Inc., USA) as an alternative to contact lens for the establishment of AK in the mouse model.

Methods: Thirty-six Balb/c mice in three groups of six mice each for two strains of Acanthamoeba were used to induce AK. Three experimental approaches used were; i) Acanthamoeba impregnated contact lens, ii) Acanthamoeba impregnated parafilm and iii) scratching followed by inoculation of Acanthamoeba suspension. In all three models, tarsorrhaphy was performed. Infection was evaluated by clinical examination and also through microscopic examination of corneal scrapings and corneal sections.

Results: AK model was successfully established with parafilm whereas only one mouse developed AK with the use of contact lens and none with scratching and Acanthamoeba inoculation.

Conclusion: The use of parafilm is convenient, reliable and cheaper and can be considered an alternative to contact lenses to induce AK in a mouse model.
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http://dx.doi.org/10.1016/j.ijmmb.2021.01.005DOI Listing
January 2021

Aspects of Point-of-Care Diagnostics for Personalized Health Wellness.

Int J Nanomedicine 2021 14;16:383-402. Epub 2021 Jan 14.

Department of Civil & Environmental Engineering, Hanyang University, Seoul 04763, Republic of Korea.

Advancements in analytical diagnostic systems for point-of-care (POC) application have gained considerable attention because of their rapid operation at the site required to manage severe diseases, even in a personalized manner. The POC diagnostic devices offer easy operation, fast analytical outcome, and affordable cost, which promote their advanced research and versatile adoptability. Keeping advantages in view, considerable efforts are being made to design and develop smart sensing components such as miniaturized transduction, interdigitated electrodes-based sensing chips, selective detection at low level, portable packaging, and sustainable durability to promote POC diagnostics according to the needs of patient care. Such effective diagnostics systems are in demand, which creates the challenge to make them more efficient in every aspect to generate a desired bio-informatic needed for better health access and management. Keeping advantages and scope in view, this mini review focuses on practical scenarios associated with miniaturized analytical diagnostic devices at POC application for targeted disease diagnostics smartly and efficiently. Moreover, advancements in technologies, such as smartphone-based operation, paper-based sensing assays, and lab-on-a-chip (LOC) which made POC more sensitive, informative, and suitable for major infectious disease diagnosis, are the main focus here. Besides, POC diagnostics based on automated patient sample integration with a sensing platform is continuously improving therapeutics interventions against specific infectious disease. This review also discussed challenges associated with state-of-the-art technology along with future research opportunities to design and develop next generation POC diagnostic systems needed to manage infectious diseases in a personalized manner.
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http://dx.doi.org/10.2147/IJN.S267212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814661PMC
January 2021

Moving beyond epidermal growth factor receptor resistance in metastatic non-small cell lung cancer - a drug development perspective.

Crit Rev Oncol Hematol 2021 Mar 20;159:103225. Epub 2021 Jan 20.

Drug Development Unit, Royal Marsden Hospital and Institute of Cancer Research, Sutton, United Kingdom. Electronic address:

Epidermal Growth Factor Receptor (EGFR) mutations are the most common targetable oncogenic driver mutation in metastatic non-small lung cancer (NSCLC). There have been significant advances in the management of metastatic EGFR-mutant NSCLC from the advent of first and second generation EGFR inhibitors to, more recently, the third-generation inhibitor osimertinib. Osimeritinib is now established as first-line therapy on the basis of improved outcomes compared to first and second generation agents. However, despite excellent initial response rates, responses may not be durable due to the development of acquired resistance. Understanding these mechanisms of resistance is critical to the development of rational drug and drug combinations capable of circumventing them. We discuss the major mechanisms of resistance to first, second and third generation EGFR TKIs. The potential of drug combinations utilising chemotherapy, immunotherapy and anti-angiogenic drugs are explored. We examine strategies to aid drug development, including circulating tumour DNA and novel trial designs.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103225DOI Listing
March 2021

WITHDRAWN: Acanthamoeba keratitis in a mouse model using a novel approach.

Indian J Med Microbiol 2020 Nov 25. Epub 2020 Nov 25.

Department of Medical Parasitology, Post Graduate Institute of Medical Education & Research, Chandigarh, India. Electronic address:

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.ijmmb.2020.11.001DOI Listing
November 2020

Automated processing of social media content for radiologists: applied deep learning to radiological content on twitter during COVID-19 pandemic.

Emerg Radiol 2021 Jan 18. Epub 2021 Jan 18.

Trauma Imaging Research and Innovation Center, Department of Radiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA, 02115, USA.

Purpose: The purpose of this study was to develop an automated process to analyze multimedia content on Twitter during the COVID-19 outbreak and classify content for radiological significance using deep learning (DL).

Materials And Methods: Using Twitter search features, all tweets containing keywords from both "radiology" and "COVID-19" were collected for the period January 01, 2020 up to April 24, 2020. The resulting dataset comprised of 8354 tweets. Images were classified as (i) images with text (ii) radiological content (e.g., CT scan snapshots, X-ray images), and (iii) non-medical content like personal images or memes. We trained our deep learning model using Convolutional Neural Networks (CNN) on training dataset of 1040 labeled images drawn from all three classes. We then trained another DL classifier for segmenting images into categories based on human anatomy. All software used is open-source and adapted for this research. The diagnostic performance of the algorithm was assessed by comparing results on a test set of 1885 images.

Results: Our analysis shows that in COVID-19 related tweets on radiology, nearly 32% had textual images, another 24% had radiological content, and 44% were not of radiological significance. Our results indicated a 92% accuracy in classifying images originally labeled as chest X-ray or chest CT and a nearly 99% accurate classification of images containing medically relevant text. With larger training dataset and algorithmic tweaks, the accuracy can be further improved.

Conclusion: Applying DL on rich textual images and other metadata in tweets we can process and classify content for radiological significance in real time.
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http://dx.doi.org/10.1007/s10140-020-01885-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811945PMC
January 2021