Publications by authors named "A U Joshi"

3,310 Publications

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A novel treatment of sialocele with sodium tetradecyl sclerotherapy.

Am J Otolaryngol 2021 Apr 7;42(5):103031. Epub 2021 Apr 7.

Division of Otolaryngology-Head and Neck Surgery, George Washington University School of Medicine & Health Sciences, Washington, DC, United States of America. Electronic address:

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http://dx.doi.org/10.1016/j.amjoto.2021.103031DOI Listing
April 2021

Exploiting Substrate Cues for Co-Culturing Cells in a Micropattern.

Langmuir 2021 Apr 19. Epub 2021 Apr 19.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.

Spatial distribution of cells and their interactions between neighboring cells in native microenvironments are of fundamental importance in determining cell fate decisions such as migration, growth, and differentiation. Controlling the spatial distribution of different cell types in defined geometries can replicate these native environments, which can be a useful model for several studies. While spatiotemporal control over multiple cell arrangements is required to achieve the complex tissue architecture, unfortunately, conventional cell patterning techniques usually allow only single patterning with a single cell type. In the present study, we introduce a simple lithographic method to pattern multiple cell types in a spatially controlled manner by utilizing the biophysical cues present at the corners of the patterned geometry. By fabricating micropatterns of different shapes, we demonstrate how the cell can be constrained to pattern along the corners of patterned geometries owing to the presence of topographical cues, leaving empty voids in the center that can be further utilized for patterning a second cell type. We also demonstrate that the cell alignment along the pattern is a dynamic process and the cells migrate from a more uniform cell-adhesive region toward the topographical cues. The cytoskeleton arrangement was geometry-dependent, which was confirmed through a series of evaluations, such as scanning electron microscopy and fluorescence microscopy. These findings have not only helped us in exploring the importance of these cues in guiding the cell fate but have also allowed us to develop a technique, which self-patterns the cells without any expensive exogenous cues and can be used as a model protocol to eventually organize cells into a specific pattern with micron-scale precision .
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http://dx.doi.org/10.1021/acs.langmuir.1c00170DOI Listing
April 2021

Elements of stress relieving strategies amongst engineering students.

Work 2021 Apr 10. Epub 2021 Apr 10.

School of Humanities and Social Sciences, Thapar Institute of Engineering and Technology, Patiala, India.

Background: Stress relieving strategies (SRS) are quite significant to get rid of stress in engineering students.

Objective: The objective of this study is to determine the SRS factors in the engineering universities in Punjab state of India. This effort also aims to check the determinants of SRS.

Methods: The data is collected through a questionnaire survey conducted on engineering students of two different universities. The collected data out of 400 surveys is subjected to factor analysis and Anova.

Results: The factor analysis exposed various factors that influence the SRS. The study has projected the effects of SRS on Gender, Age, engineering streams, Nature of Universities.

Conclusions: It is found that the SRS in students is partially influenced by Engineering Streams and Gender of the Engineering Students.
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http://dx.doi.org/10.3233/WOR-213444DOI Listing
April 2021

Evaluation of Benzamide-chalcone Derivatives as EGFR/CDK2 inhibitor: Synthesis, in-vitro Inhibition, and Molecular Modeling Studies.

Anticancer Agents Med Chem 2021 Apr 14. Epub 2021 Apr 14.

Department of Pharmaceutical Chemistry, Prin. K. M. Kundnani College of Pharmacy, Mumbai 400005. India.

Background: EGFR (Epidermal Growth Factor Receptor) and CDK2 (Cyclin Dependent Kinase 2) are important targets in the treatment of many solid tumors and different ligands of these receptors share many common structural features.

Objective: The study involved synthesis of benzamide-substituted chalcones and determination of their antiproliferative activity as well as preliminary evaluation of EGFR and CDK2 inhibitory potential using both receptor binding and computational methods.

Methods: We synthesized 13 benzamide-substituted chalcone derivatives and tested their antiproliferative activity against MCF-7, HT-29 and U373MG cell-lines using Sulforhodamine B Assay. Four compounds were examined for activity against EGFR and CDK2 kinase. The compounds were docked into both EGFR and CDK2 using Glide software. The stability of the interactions for most active compound was evaluated by Molecular Dynamics Simulation using Desmond software. Molecular Docking studies on mutant EGFR (T790M, T790M/L858R, and T790M/C797S) were also carried out.

Results: From the SRB assay, we concluded that compounds 1g, and 1k were effective in inhibiting the growth of MCF-7 cell line whereas the other compounds were moderately active. Most compounds were either moderately active or inactive on U373 MG and HT-29 cell line. Compounds 1g and 1k showed good inhibitory activity against CDK2 kinase while 1d and 1f were moderately active. Compounds 1d, 1f, 1g, and 1k were moderately active against EGFR kinase. Molecular docking reveals involvement of one hydrogen bond with Met793 in binding with EGFR however; it was not stable during simulation and these compounds bind to the receptor mainly via hydrophobic contacts. This fact also points towards a different orientation of the inhibitor within the active site of EGFR kinase. Binding mode analysis for CDK2 inhibition studies indicate that hydrogen bonding interaction with Lys 33 and Leu83 are important for the activity. These interactions were found to be stable throughout the simulation. Considering the results for wild-type EGFR inhibition, the docking studies on mutants were performed and which indicate that the compounds bind to the mutant EGFR but the amino acid residues involved are similar to the wild-type EGFR and therefore, the selectivity seems to be limited.

Conclusion: These benzamide-substituted chalcone derivatives will be useful as lead molecules for the further development of newer inhibitors of EGFR and/or CDK2 kinases.
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http://dx.doi.org/10.2174/1871520621666210415091359DOI Listing
April 2021

Outcomes of patients hospitalized for acute pulmonary embolism by obstructive sleep apnea status.

Pulm Circ 2021 Apr-Jun;11(2):2045894021996224. Epub 2021 Mar 27.

Institute of Cardiovascular Medicine, Section of Advanced Heart Failure/Transplant/MCS and Pulmonary Hypertension, Allegheny General Hospital, Pittsburgh, PA, USA.

Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) is increasingly recognized in the aging population, especially with the rising obesity epidemic. The impact of OSA on inpatient mortality in PE is not well understood. We used the Nationwide Inpatient Sample databases from 2005 to 2016 to identify 755,532 acute PE patients (age≥18 years). Among these, 61,050 (8.1%) were OSA+. Temporal trends in length of stay, inpatient mortality, and its association with OSA in PE patients were analyzed. The proportion of PE patients who were OSA+ increased from 2005 to 2016. OSA+ PE patients were younger and predominantly men. Despite a higher prevalence of traditional risk factors for inpatient mortality in OSA+ patients, OSA was associated with a lower risk of mortality in PE patients (odds ratio, 95% confidence interval; : unadjusted 0.56, 0.53-0.58;  < 0.0001 and adjusted 0.55, 0.52-0.58;  < 0.0001). Overall mortality and length of stay in PE patients decreased over time. Relative to OSA- patients, there was a slight increase in mortality among OSA+ PE patients over time, although the length of stay remained unchanged between the two groups. In conclusion, OSA+ PE patients had a lower inpatient mortality compared to OSA- patients despite a higher prevalence of traditional mortality risk factors. Secondary pulmonary hypertension related to OSA with preconditioning of the right ventricle to elevated afterload may potentially explain the protective effect of OSA on mortality in PE. However, mechanistic studies need to further elucidate the links behind this association.
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http://dx.doi.org/10.1177/2045894021996224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013707PMC
March 2021

In-silico design of a multivalent epitope-based vaccine against Candida auris.

Microb Pathog 2021 Apr 18;155:104879. Epub 2021 Apr 18.

Department of Molecular Biology and Genetic Engineering, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, 144401, Punjab, India. Electronic address:

Candida auris is a rapidly emerging human pathogenic fungus with a high mortality rate. Recent report suggests that the new clinical isolates are showing resistance to the major classes of antifungal drugs. Due to the emergence of drug resistance, it becomes imperative to seek novel therapies for the treatment of C. auris. The potent vaccine could be one of the promising strategies for recalcitrant and multidrug-resistant pathogens. Using in silico approach we designed a novel multivalent vaccine against C. auris. We have selected the agglutinin-like sequence-3 (Als3) an adhesion protein, involved in virulence. The Als3p protein of C. auris was targeted to predict T cell and B cell epitopes. Epitopes which were found to be non-toxic, non-allergenic, highly conserved, and antigenic and could induce interferon-γ synthesis were selected for vaccine design. The selected epitopes were linked with suitable adjuvants to construct the final vaccine. The vaccine construct was predicted to be stable, soluble, antigenic, non-allergic with desirable physicochemical properties. We also constructed the 3D model of the vaccine and validated it with the Ramachandran plot. The ability of the vaccine construct to interact with Toll-like receptor (TLR) and major histocompatibility complex (MHC) was determined by molecular docking experiments. The binding energy of the vaccine construct with the TLR and MHC were found to be stable as predicted by molecular dynamics simulation. Further, in-silico cloning analysis showed that the vaccine construct can be successfully cloned and expressed in E. coli. Based on the results, we surmise that our candidate vaccine can be used as an alternative therapy for the treatment of C. auris. However, the efficacy and the safety of the vaccine model need to be determined by performing in vivo studies.
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http://dx.doi.org/10.1016/j.micpath.2021.104879DOI Listing
April 2021

Catastrophic Antiphospholipid Syndrome in Immune Thrombocytopenic Purpura - Beyond Tenuous Concomitance!

Indian J Nephrol 2020 Nov-Dec;30(6):424-426. Epub 2020 Nov 19.

Department of Hematology, Army Hospital (Research and Referral), New Delhi, India.

Significance of antiphospholipid antibodies in immune thrombocytopenic purpura is debatable and pose a diagnostic and therapeutic dilemma. Catastrophic antiphospholipid syndrome is a rare life-threatening entity, occurring in patients with antiphospholipid syndrome, usually after a triggering event. We describe an adult lady of chronic immune thrombocytopenic purpura (in remission) with antiphospholipid antibodies, who presented with rapidly progressive renal failure and had primary antiphospholipid syndrome nephropathy. The index manuscript titled exemplifies the fact that although the presence of APLA in ITP is known, however, management in the absence of clinical event remains debatable and may carry a future risk of thrombotic event/s mandating close monitoring with a high index of suspicion.
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http://dx.doi.org/10.4103/ijn.IJN_188_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023023PMC
November 2020

Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals.

J Natl Cancer Inst 2021 Apr 10. Epub 2021 Apr 10.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Background: Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest.

Methods: We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12,712 individuals in the ASPirin in Reducing Events in the Elderly trial. We evaluated incident melanomas diagnosed during the trial and prevalent melanomas diagnosed pre-enrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per standard deviation [SD]), and categorical (low-risk [0-20%], medium-risk [21-80%], high-risk [81-100%] groups) with incident melanoma. Logistic regression examined the association between PRS and prevalent melanoma.

Results: At baseline, mean participant age was 75 years; 55.0% were female, and 528 (4.2%) had prevalent melanomas. During follow-up (median = 4.7 years), 120 (1.0%) incident cutaneous melanomas occurred, 98 of which were in participants with no history. PRS was associated with incident melanoma (hazard ratio = 1.46 per SD, 95% confidence interval [CI] = 1.20-1.77) and prevalent melanoma (odds ratio [OR]=1.55 per SD, 95% CI = 1.42-1.69). Participants in the highest-risk PRS group had increased risk compared to the low-risk group for incident (OR = 2.51, 95% CI = 1.28-4.92) and prevalent (OR = 3.66, 95% CI = 2.69-5.05). When stratifying by sex, only males had an association between the PRS and incident melanoma, whereas both sexes had an association between the PRS and prevalent melanoma.

Conclusion: A genomic risk score is associated with melanoma risk in older individuals, and may contribute to targeted surveillance.
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http://dx.doi.org/10.1093/jnci/djab076DOI Listing
April 2021

Rational use of Ashwagandha in Ayurveda (Traditional Indian Medicine) for health and healing.

J Ethnopharmacol 2021 Apr 5:114101. Epub 2021 Apr 5.

Ozone Pharmaceutical Ltd., Ozone House, Block A-3, 1 LSC, Janak Puri, New Delhi, India.

Ethnopharmacological Relevance: Withania somnifera (L.) Dunal (Physalis somnifera L.) is a fairly known perennial shrub of Solanaceae family, and is used in Ayurveda- Traditional Indian Medicine (TIM), since ancient times. It is well known as Ashwagandha in Sanskrit language in Ayurvedic classics. Its Mula (root) is recommended for health and healing, and the number of single and compound formulation is prescribed rationally. It is believed that the species name-somnifera is coined based on popular use to "induce sleep" in Ayurveda.

Aim Of The Study: The present study was aimed to bring out the experience-based traditional uses of Ashwagandha for health and healing with an emphasis on the pharmacological and biochemical scientific evidences to corroborate them. The scientific evidences have been explored from the national and international publications.

Materials And Method: A comprehensive literary search of Ayurvedic classics was carried out systematically regarding Ashwagandha for its rationality behind the traditional uses. To excavate the subject matter, the original Ayurvedic scriptures and several standard Ayurvedic texts of different period was studied insightfully for meaningful contribution. It is to be noted that the primary source of knowledge was considered in writing this manuscript without any biased attitude. The available literature on Ashwagandha was also searched to ascertain the basis of scientific Latin name and correct identity. The Ayurvedic Pharmacopoeia and other relevant scientific works were also taken into consideration to make the subject matter more clearly to the scientific world. For the scientific evidence of the uses, the international and national Journals and other published material were also searched to make it inquisitiveness to the scholars interested in Ayurvedic medicinal plants.

Results: The present paper throws ancient luminosity behind the therapeutic uses of one of the promising plant drug i.e., Ashwagandha of ancient India even to the present time. The scientific evidences corroborate the rationality ascribed in available Ayurvedic classics of various period of India has been gained.

Conclusion: The study explores that the first reference of Ashwagandha with its significant nomenclature, useful part, properties, action, and eloquent uses has its footprint in the original texts of Ayurveda. In later works enhanced knowledge with traditional uses continued even today. Several single and compound formulations have been found to maintain the health and to alleviate the disorders rationally. It is worthy to note here that the scientific evidences corroborate the uses practiced in Ayurveda.
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http://dx.doi.org/10.1016/j.jep.2021.114101DOI Listing
April 2021

Psychometric properties of FACIT-Fatigue in systemic lupus erythematosus: a pooled analysis of three phase 3 randomised, double-blind, parallel-group controlled studies (BLISS-SC, BLISS-52, BLISS-76).

J Patient Rep Outcomes 2021 Apr 8;5(1):33. Epub 2021 Apr 8.

Optum, Johnston, RI, USA.

Background: Fatigue is a key symptom in patients with systemic lupus erythematosus (SLE), and regulatory bodies recommend its assessment in clinical trials of SLE therapies.

Methods: This post hoc pooled analysis of the three BeLimumab In Subjects with Systemic lupus erythematosus (BLISS) Phase 3 randomised, double-blind, parallel-group controlled trials evaluated the measurement properties of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Patients (N = 2520) completed the FACIT-Fatigue every 4 weeks from baseline until the end of each study period. Internal consistency, test-retest reliability, convergent validity, and ability to detect changes in SLE were evaluated for the FACIT-Fatigue.

Results: The FACIT-Fatigue showed good internal consistency reliability (Cronbach's alpha > 0.90), very good test-retest reliability (0.76 ≤ intraclass correlation coefficient ≤ 0.92), and moderate-strong convergent validity (0.49 ≤ |r| ≤ 0.86) against scale and summary measure scores from the Short Form 36 Health Survey Version 2. Correlations between FACIT-Fatigue and British Isles Lupus Assessment Group (BILAG) General/Musculoskeletal scores (0.24 ≤ |r| ≤ 0.43) supported convergent validity. Correlations between FACIT-Fatigue and the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores and SLE annualised flare rate were weak but in the expected direction (ranging from - 0.02 to - 0.25). Known-groups validity testing showed that the FACIT-Fatigue can significantly discriminate between patient groups with differing scores for SELENA-SLEDAI, BILAG (General and Musculoskeletal) ratings, and Physician's Global Assessment (PGA). Patients showing improvement in PGA and meeting the BILAG responder criteria had significantly higher mean improvement in FACIT-Fatigue scores than those without improvements in either measure (Week 52 mean score difference [95% confidence interval]: - 4.0 [- 5.0, - 3.0] and -2.2 [-3.1, -1.2], respectively; both p < 0.0001). The range of important (i.e. meaningful) change in FACIT-Fatigue, based on multiple anchors, was 3-6 points.

Conclusions: The FACIT-Fatigue demonstrated adequate psychometric properties in patients with SLE. The body of evidence from the three BLISS trials (both pooled and individually) supports the FACIT-Fatigue as a reliable and valid measure of SLE-related fatigue in clinical trials.

Clinical Trial Identifiers: BLISS-SC (NCT01484496), BLISS-52 (NCT00424476), and BLISS-76 (NCT00410384).
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http://dx.doi.org/10.1186/s41687-021-00298-xDOI Listing
April 2021

Advanced molecular pathology for rare tumours: A national feasibility study and model for centralised medulloblastoma diagnostics.

Neuropathol Appl Neurobiol 2021 Apr 7. Epub 2021 Apr 7.

Newcastle University Centre for Cancer, Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

Aims: Application of advanced molecular pathology in rare tumours is hindered by low sample numbers, access to specialised expertise/technologies, and tissue/assay QC and rapid reporting requirements. We assessed the feasibility of co-ordinated real-time centralised pathology review (CPR), encompassing molecular diagnostics and contemporary genomics (RNA-seq/DNA methylation array). Methods This nationwide trial in medulloblastoma (<80 UK diagnoses/year) introduced a national reference centre (NRC), and assessed its performance and reporting to World Health Organisation standards. Paired frozen/FFPE tumour material were co-submitted from 135 patients (16 referral centres).

Results: Complete CPR diagnostics were successful for 88% (120/135). Inadequate sampling was the most common cause of failure; biomaterials were typically suitable for methylation-array (129/135, 94%), but frozen tissues commonly fell below RNA-seq QC requirements (53/135, 39%). Late reporting was most often due to delayed submission. CPR assigned or altered histological variant (vs. local diagnosis) for 40/135 tumours (30%). Benchmarking/QC of specific biomarker assays impacted test results; iFISH most accurately identified high-risk MYC/MYCN amplification (20/135, 15%), while combined methods (CTNNB1/chr6 status, methylation-array subgrouping) best-defined favourable-risk WNT tumours (14/135; 10%). Engagement of a specialist pathologist panel was essential for consensus assessment of histological variants and immunohistochemistry. Overall, CPR altered clinical risk-status for 29% of patients.

Conclusion: National real-time CPR is feasible, delivering robust diagnostics to WHO criteria and assignment of clinical risk-status, significantly altering clinical management. Recommendations and experience from our study are applicable to advanced molecular diagnostics systems, both local and centralised, across rare tumour types, enabling their application in biomarker-driven routine diagnostics and clinical/research studies.
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http://dx.doi.org/10.1111/nan.12716DOI Listing
April 2021

Multiple C2 domain-containing transmembrane proteins promote lipid droplet biogenesis and growth at specialized ER subdomains.

Mol Biol Cell 2021 Apr 7:mbcE20090590. Epub 2021 Apr 7.

Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill.

Lipid droplets (LDs) are neutral lipid-containing organelles enclosed in a single monolayer of phospholipids. LD formation begins with the accumulation of neutral lipids within the bilayer of the endoplasmic reticulum (ER) membrane. It is not known how the sites of formation of nascent LDs in the ER membrane are determined. Here we show that multiple C2 domain-containing transmembrane proteins, MCTP1 and MCTP2, are at sites of LD formation in specialized ER subdomains. We show that the transmembrane domain (TMD) of these proteins is similar to a reticulon homology domain. Like reticulons, these proteins tubulate the ER membrane and favor highly curved regions of the ER. Our data indicate that the MCTP TMDs promote LD biogenesis, increasing LD number. MCTPs co-localize with seipin, a protein involved in LD biogenesis, but form more stable microdomains in the ER. The MCTP C2 domains bind charged lipids and regulate LD size, likely by mediating ER-LD contact sites. Together, our data indicate that MCTPs form microdomains within ER tubules that regulate LD biogenesis, size, and ER-LD contacts. Interestingly, MCTP punctae colocalized with other organelles as well, suggesting that these proteins may play a more general role in linking tubular ER to organelle contact sites. [Media: see text] [Media: see text].
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http://dx.doi.org/10.1091/mbc.E20-09-0590DOI Listing
April 2021

Facilitator lessons from online psychoeducational group for relational well-being in India during COVID-19 pandemic.

J Fam Ther 2021 Apr 15;43(2):314-328. Epub 2021 Feb 15.

Research officer, Sukoon, Tata Institute of Social Sciences Mumbai India.

The COVID-19 pandemic has affected the mental health of individuals, along with their couple and familial relationships, necessitating an effective response. Teletherapy offers an option to address these relationship concerns amidst pandemic-specific mobility restriction. Against this setting, Sukoon, a project of Tata Institute of Social Sciences, India, initiated a five-session online psychoeducational group series on relational wellbeing. This paper explores facilitator's reflections and learnings based on session documentation and facilitator notes. Preparing well and selecting participants carefully for online psychoeducational groups was critical to success. Effectiveness was enhanced by flexibly adapting the therapy process (didactic and interactive elements) to fit online delivery and the cultural context. Identifying the potential of online psychoeducational groups for relational wellbeing could make it a valuable addition to the COVID-19 pandemic mental health response toolkit.

Practitioner Points: Effective preparation and careful selection of group members is key to the success of therapist facilitated online psychoeducational groups.Psychoeducational groups comprising didactic and interactive elements are more suitable for effective online group processes.Use of co-facilitators managing various channels of communication (audio, chat) is important. Group facilitators need to be cognisant of challenges of online medium and address them in an ongoing manner.
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http://dx.doi.org/10.1111/1467-6427.12337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013498PMC
April 2021

Challenges for extending radiology services during COVID-19 pandemic.

Indian J Radiol Imaging 2021 Jan 23;31(Suppl 1):S213-S215. Epub 2021 Jan 23.

Department of Radiology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, Maharashtra, India. E-mail:

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http://dx.doi.org/10.4103/ijri.IJRI_749_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996685PMC
January 2021

Where have all the diseases gone during the COVID-19 pandemic?

Indian J Radiol Imaging 2021 Jan 23;31(Suppl 1):S119-S121. Epub 2021 Jan 23.

Department of Radiology, Lokmanya Tilak Municipal Medical College and Hospital, Mumbai, Maharashtra, India.

This article focuses on a marked drop in volumes in the lockdown period during the COVID-19 pandemic across all modalities X-ray, sonography, CT scan and MRI scans and compares the volumes of data between a private and public hospital in Mumbai. This trend has been witnessed globally also. Even with easing of lockdown this has not reflected in an increase in numbers. Imaging volumes of a 1900-bed public hospital and a 220-bed private hospital in Mumbai were collated for all modalities, i.e., X-ray, sonography, CT and MRI for the months January, February 2020- Prelockdown, March 2020 Peri-lockdown, April, May 2020- Lockdown, June Unlock 1.0, July Unlock 2.0. The imaging volumes during lockdown, Unlock, were compared with prelockdown values. It was initially felt that this was due to a fear of visiting hospitals that are considered hotbeds of SARS-CoV-2. However, the same status has persisted over the 2 months of lockdown and the 2 months of unlocking. What is the cause of this huge drop in imaging volumes?
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http://dx.doi.org/10.4103/ijri.IJRI_721_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996705PMC
January 2021

Does CT help in reducing RT-PCR false negative rate for COVID-19?

Indian J Radiol Imaging 2021 Jan 23;31(Suppl 1):S80-S86. Epub 2021 Jan 23.

Department of Radiodiagnosis, LTMMC Sion Hospital, Mumbai, India.

Background: Early detection is the key to contain the ongoing pandemic. The current gold standard to detect SARS CoV2 is RT-PCR. However, it has a high false negative rate and long turnaround time.

Purpose: In view of the high sensitivity of CT in detection of lower respiratory tract pathologies, a study of 2581 patients comparing RT-PCR status with CT findings was undertaken to see if it augments the diagnostic performance.

Materials And Methods: A multi centre prospective study of consecutive cases was conducted. All CT studies suggestive of COVID 19 pneumonia were collated and evaluated independently by three Radiologists to confirm the imaging diagnosis of COVID-19 pneumonia. The RT-PCR values were retrospectively obtained, based on the RT-PCR values, CT studies were categorised into three subgroups, positive, negative and unknown. CT features from all three groups were compared to evaluate any communality or discordance.

Results: Out of the 2581 patients with positive CT findings for COVID pneumonia, 825 were females and 1,756 were males in a wide age group of 28-90 years. Predominant CT features observed in all the subgroups were Ground glass densities 94.8%, in mixed distribution (peripheral and central) (59.12%), posterior segments in 92% and multilobar involvement in 70.9%. The CT features across the three subgroups were statistically significant with a value <0.001.

Conclusion: There was a communality of CT findings regardless of RT-PCR status. In a pandemic setting ground glass densities in a subpleural, posterior and basal distribution are indicative of COVID 19. Thus CT chest in conjunction to RT PCR augments the diagnosis of COVID 19 pneumonia; utilization of CT chest may just be the missing link in closing this pandemic.
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http://dx.doi.org/10.4103/ijri.IJRI_739_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996706PMC
January 2021

Incidental chest computed tomography findings in asymptomatic Covid-19 patients. A multicentre Indian perspective.

Indian J Radiol Imaging 2021 Jan 23;31(Suppl 1):S45-S52. Epub 2021 Jan 23.

Department of Radiology, Global Hospitals, Mumbai, Maharashtra, India.

In December 2019, an unprecedented outbreak of pneumonia of unknown etiology emerged called COVID-19. A vast number of people affected by this disease are asymptomatic and yet contagious with up to 79% of COVID-19 infections reportedly caused by undocumented infections. Surprisingly, these asymptomatic subjects are also known to quietly harbor pneumonia changes on CT scans. RT-PCR, the definitive test for COVID-19, maybe false negative in patients with COVID-19 pneumonia on CT. Incidental findings highly suspicious of COVID-19 pneumonia on CT chest of asymptomatic patients may increase as the community transmission of the virus rises and isolation restrictions are released. It is advisable to be aware of its appearances and the challenges associated with it.
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http://dx.doi.org/10.4103/ijri.IJRI_479_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996682PMC
January 2021

Maternal allergic inflammation in rats impacts the offspring perinatal neuroimmune milieu and the development of social play, locomotor behavior, and cognitive flexibility.

Brain Behav Immun 2021 Mar 30. Epub 2021 Mar 30.

Department of Psychology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA. Electronic address:

Maternal systemic inflammation increases risk for neurodevelopmental disorders like autism, ADHD, and schizophrenia in offspring. Notably, these disorders are male-biased. Studies have implicated immune system dysfunction in the etiology of these disorders, and rodent models of maternal immune activation provide useful tools to examine mechanisms of sex-dependent effects on brain development, immunity, and behavior. Here, we employed an allergen-induced model of maternal inflammation in rats to characterize levels of mast cells and microglia in the perinatal period in male and female offspring, as well as social, emotional, and cognitive behaviors throughout the lifespan. Adult female rats were sensitized to ovalbumin (OVA), bred, and challenged intranasally on gestational day 15 of pregnancy with OVA or saline. Allergic inflammation upregulated microglia in the fetal brain, increased mast cell number in the hippocampus on the day of birth, and conferred region-, time- and sex- specific changes in microglia measures. Additionally, offspring of OVA-exposed mothers subsequently exhibited abnormal social behavior, hyperlocomotion, and reduced cognitive flexibility. These data demonstrate the long-term effects of maternal allergic challenge on offspring development and provide a basis for understanding neurodevelopmental disorders linked to maternal systemic inflammation in humans.
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http://dx.doi.org/10.1016/j.bbi.2021.03.025DOI Listing
March 2021

Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations.

Oncotarget 2021 Mar 16;12(6):578-588. Epub 2021 Mar 16.

Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment Research Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra 410210, India.

Introduction: Unlike lung adenocarcinoma patients, there is no FDA-approved targeted-therapy likely to benefit lung squamous cell carcinoma patients.

Materials And Methods: We performed survival analyses of lung squamous cell carcinoma patients harboring therapeutically relevant alterations identified by whole exome sequencing and mass spectrometry-based validation across 430 lung squamous tumors.

Results: We report a mean of 11.6 mutations/Mb with a characteristic smoking signature along with mutations in and among lung squamous cell carcinoma patients of Indian descent. In addition, therapeutically relevant mutations occur in 5.8% patients, significantly higher than as reported among Caucasians. In overall, our data suggests 13.5% lung squamous patients harboring druggable mutations have lower median overall survival, and 19% patients with a mutation in at least one gene, known to be associated with cancer, result in significantly shorter median overall survival compared to those without mutations.

Conclusions: We present the first comprehensive landscape of genetic alterations underlying Indian lung squamous cell carcinoma patients and identify and as potentially important therapeutic and prognostic target.
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http://dx.doi.org/10.18632/oncotarget.27905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984830PMC
March 2021

A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants.

bioRxiv 2021 Mar 24. Epub 2021 Mar 24.

The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.

One Sentence Summary: Protection against SARS-CoV-2 variants by a potently neutralizing vaccine-induced human monoclonal antibody.
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http://dx.doi.org/10.1101/2021.03.24.436864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010723PMC
March 2021

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings.

Medicine (Baltimore) 2021 Apr;100(13):e25115

Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

Abstract: Immune checkpoint inhibitors (ICIs) are rapidly being incorporated as treatment option either alone or in combination with chemotherapy in most of the solid tumors. Since there is very limited data of ICI in patients with poor performance status (PS) from the real world settings, we performed a retrospective audit of patients who received ICI and report the analysis based on ECOG PS of these patients.This study is a retrospective audit of a prospectively collected database of patients receiving ICIs for advanced solid tumors in any line between August 2015 and November 2018 at Tata Memorial Hospital, Mumbai, India. All statistical calculations were performed using SPSS statistical software for windows version 20.0.A total of 155 patients who received ICIs during the specified period were evaluated for this study. Baseline ECOG PS 0-1 (n = 103, 66.4%) patients was associated with median OS 9.1 (95% CI [confidence interval], 4.4-NR) months when compared to ECOG 2-4 (n = 52, 33.5%) which had a median OS of 2.9 (95% CI; 1.8-5.5) months (HR, 1.7, 95% CI, 1.1-2.7, log rank P = .017). The disease control rate for the poor PS group was 34.6%. However, 27.3% patients (95% CI: 20.3-34.3) were still alive at 1 year. Median OS in patients with PS 2 was 3.7 months (95% CI: 0-11.6) as compared to 1.8 months (95% CI: 0.2-3.4) for those with PS 3-4 (HR-2.0; 95% CI: 1.0-3.9, P = .041). The tolerance to ICIs was good with no grade 3/4 toxicities in 44 (84.6%) patients.Immune checkpoint inhibitors are a safe and effective therapeutic option even in solid tumor patients with poor performance status.
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http://dx.doi.org/10.1097/MD.0000000000025115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021372PMC
April 2021

ASSOCIATION OF HYPERGLYCAEMIA WITH HOSPITAL MORTALITY IN NONDIABETIC COVID-19 PATIENTS: A COHORT STUDY.

Diabetes Metab 2021 Mar 26:101254. Epub 2021 Mar 26.

M&H Research, LLC, San Antonio, Texas, USA. Electronic address:

Objective: Diabetes is a known risk factor for mortality in Coronavirus disease 2019 (COVID-19) patients. Our objective was to identify prevalence of hyperglycaemia in COVID-19 patients with and without prior diabetes and quantify its association with COVID-19 disease course.

Research Design And Methods: This observational cohort study included all consecutive COVID-19 patients admitted to John H Stroger Jr. Hospital, Chicago, IL from March 15, 2020 to May 3, 2020 and followed till May 15, 2020. The primary outcome was hospital mortality, and the studied predictor was hyperglycaemia [any blood glucose ≥ 7.78 mmol/L (140 mg/dL) during hospitalization].

Results: Of the 403 COVID-19 patients studied, 51 (12.7%) died; 335 (83.1%) were discharged while 17 (4%) were still in hospital. Hyperglycaemia occurred in 228 (56.6%) patients; 83 of these hyperglycaemic patients (36.4%) had no prior history of diabetes. Compared to the reference group no-diabetes / no-hyperglycaemia patients the no-diabetes / hyperglycaemia patients showed higher mortality [1.8% versus 20.5%, adjusted odds ratio 21.94 (95% confidence interval 4.04-119.0), P <  0.001]; improved prediction of death (P =  0.01) and faster progression to death (P <  0.01). Hyperglycaemia within the first 24 and 48 hours was also significantly associated with mortality (odds ratio 2.15 and 3.31, respectively).

Conclusions: Hyperglycaemia without prior diabetes was common (20.6% of hospitalized COVID-19 patients) and was associated with an increased risk of and faster progression to death. Development of hyperglycaemia in COVID-19 patients who do not have diabetes is an early indicator of progressive disease.
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http://dx.doi.org/10.1016/j.diabet.2021.101254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994287PMC
March 2021

Spectroscopic Studies of Synthetic Methylaluminoxane; Structure of Methylaluminoxane Activators.

Chemistry 2021 Mar 29. Epub 2021 Mar 29.

University of Victoria Faculty of Science, Chemistry, CANADA.

Hydrolysis of trimethylaluminum (Me 3 Al) in polar solvents can be monitored by electrospray ionization mass spectrometry (ESI-MS) using the donor additive octamethyltrisiloxane [(Me 3 SiO) 2 SiMe 2 , OMTS]. Using hydrated salts, hydrolytic methylaluminoxane (h-MAO) features different anion distributions, depending on the conditions of synthesis, and different activator contents as measured by NMR spectroscopy. Non-hydrolytic MAO was prepared using trimethylboroxine. The properties of this material, which contains incorporated boron, differ significantly from h-MAO. In the case of MAO prepared by direct hydrolysis, oligomeric anions are observed to rapidly form, and then more slowly evolve into a mixture dominated by an anion with m/z 1375 with formula [(MeAlO) 16 (Me 3 Al) 6 Me] - . Theoretical calculations predict that sheet structures with composition (MeAlO) n (Me 3 Al) m are favored over other motifs for MAO in the size range suggested by the ESI-MS experiments. A possible precursor to the m/z 1375 anion is a local minimum based on the free energy released upon hydrolysis of Me 3 Al.
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http://dx.doi.org/10.1002/chem.202100271DOI Listing
March 2021

Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms.

J Exp Med 2021 Jun;218(6)

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.

Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype. Using single-cell RNA sequencing of human AAA tissues, we identified increased JMJD3 in aortic monocyte/macrophages resulting in up-regulation of an inflammatory immune response. Mechanistically, we report that interferon-β regulates Jmjd3 expression via JAK/STAT and that JMJD3 induces NF-κB-mediated inflammatory gene transcription in infiltrating aortic macrophages. In vivo targeted inhibition of JMJD3 with myeloid-specific genetic depletion (JMJD3f/fLyz2Cre+) or pharmacological inhibition in the elastase or angiotensin II-induced AAA model preserved the repressive H3K27me3 on inflammatory gene promoters and markedly reduced AAA expansion and attenuated macrophage-mediated inflammation. Together, our findings suggest that cell-specific pharmacologic therapy targeting JMJD3 may be an effective intervention for AAA expansion.
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http://dx.doi.org/10.1084/jem.20201839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008365PMC
June 2021

Biatrial Drainage of the Right Superior Vena Cava: Imaging Findings.

Radiol Cardiothorac Imaging 2020 Dec 10;2(6):e200414. Epub 2020 Dec 10.

Division of Pediatric Cardiology, Department of Pediatrics, University of Texas Health Science Center at Houston, 7000 Fannin Suite 1200, Houston, TX 77030 (M.D.P.); Division of Pediatric Cardiology, Department of Pediatrics (S.B., A.L.D., J.C.L.), Section of Pediatric Radiology, Department of Radiology (S.B., A.L.D., A.J., J.C.L., M.G.M.), and Division of Cardiothoracic Radiology, Department of Radiology (M.G.M., P.P.A.), Michigan Congenital Heart Center, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Mich.

Biatrial drainage of the right superior vena cava (SVC) is a rare form of interatrial shunting that can have substantial clinical consequences. Cross-sectional imaging techniques (CT and MRI) are well suited for evaluation and surgical planning. This review article focuses on the embryologic development, hemodynamics, and imaging features to enable a timely diagnosis. Biatrial drainage of the right SVC has important clinical implications, and knowledge of its imaging appearance and hemodynamics is essential in diagnosis and treatment planning. © RSNA, 2020.
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http://dx.doi.org/10.1148/ryct.2020200414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977811PMC
December 2020

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in a Community-Based Cohort: Data From the Washington, D.C. Cardiovascular Health and Needs Assessment.

Front Cardiovasc Med 2021 10;8:599341. Epub 2021 Mar 10.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, United States.

Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar Fluorodeoxyglucose (FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort. Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity. AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (β = 0.41, = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity. AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.
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http://dx.doi.org/10.3389/fcvm.2021.599341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988194PMC
March 2021

Pregnancy Outcomes and Blood Pressure Visit-to-Visit Variability and Level in Three Less-Developed Countries.

Hypertension 2021 May 29;77(5):1714-1722. Epub 2021 Mar 29.

Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine (L.A.M., H.L.N., A.H.S., P.v.D.), King's College London, United Kingdom.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16851DOI Listing
May 2021

Empyema thoracis: an unreported complication of an infected renal cyst.

ANZ J Surg 2021 Mar 26. Epub 2021 Mar 26.

Department of Cardiothoracic Surgery, The Townsville Hospital, Townsville, Queensland, Australia.

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http://dx.doi.org/10.1111/ans.16783DOI Listing
March 2021

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study.

Authors:

Br J Surg 2021 Mar 24. Epub 2021 Mar 24.

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling.

Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty.

Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year.

Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
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http://dx.doi.org/10.1093/bjs/znab101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995808PMC
March 2021