Evaluation of Host Protein Biomarkers by ELISA From Whole Lysed Peripheral Blood for Development of Diagnostic Tests for Active Tuberculosis

Tuberculosis (TB) remains a significant global health crisis and the number one cause of death for an infectious disease. The health consequences in high-burden countries are significant. Barriers to TB control and eradication are in part caused by difficulties in diagnosis. Improvements in diagnosis are required for organisations like the World Health Organisation (WHO) to meet their ambitious target of reducing the incidence of TB by 50% by the year 2025, which has become hard to reach due to the COVID-19 pandemic. Development of new tests for TB are key priorities of the WHO, as defined in their 2014 report for target product profiles (TPPs). Rapid triage and biomarker-based confirmatory tests would greatly enhance the diagnostic capability for identifying and diagnosing TB-infected individuals. Protein-based test methods e.g. lateral flow devices (LFDs) have a significant advantage over other technologies with regard to assay turnaround time (minutes as opposed to hours) field-ability, ease of use by relatively untrained staff and without the need for supporting laboratory infrastructure. Here we evaluate the diagnostic performance of nine biomarkers from our previously published biomarker qPCR validation study; CALCOCO2, CD274, CD52, GBP1, IFIT3, IFITM3, SAMD9L, SNX10 and TMEM49, as protein targets assayed by ELISA. This preliminary evaluation study was conducted to quantify the level of biomarker protein expression across latent, extra-pulmonary or pulmonary TB groups and negative controls, collected across the UK and India, in whole lysed blood samples (WLB). We also investigated associative correlations between the biomarkers and assessed their suitability for ongoing diagnostic test development, using receiver operating characteristic/area under the curve (ROC) analyses, singly and in panel combinations. The top performing single biomarkers for pulmonary TB versus controls were CALCOCO2, SAMD9L, GBP1, IFITM3, IFIT3 and SNX10. TMEM49 was also significantly differentially expressed but downregulated in TB groups. CD52 expression was not highly differentially expressed across most of the groups but may provide additional patient stratification information and some limited use for incipient latent TB infection. These show therefore great potential for diagnostic test development either in minimal configuration panels for rapid triage or more complex formulations to capture the diversity of disease presentations

Botany, chemistry, and pharmaceutical significance of Sida cordifolia: a traditional medicinal plant

Sida cordifolia Linn. belonging to the family, Malvaceae has been widely employed in traditional medications in many parts of the world including India, Brazil, and other Asian and African countries. The plant is extensively used in the Ayurvedic medicine preparation. There are more than 200 plant species within the genus Sida, which are distributed predominantly in the tropical regions. The correct taxonomic identification is a major concern due to the fact that S. cordifolia looks morphologically similar with its related species. It possesses activity against various human ailments, including cancer, asthma, cough, diarrhea, malaria, gonorrhea, tuberculosis, obesity, ulcer, Parkinson’s disease, urinary infections, and many others. The medical importance of this plant is mainly correlated to the occurrence of diverse biologically active phytochemical compounds such as alkaloids, flavonoids, and steroids. The major compounds include β-phenylamines, 2-carboxylated tryptamines, quinazoline, quinoline, indole, ephedrine, vasicinone, 5-3-isoprenyl flavone, 5,7-dihydroxy-3-isoprenyl flavone, and 6-(isoprenyl)- 3-methoxy- 8-C-β-D-glucosyl-kaempferol 3-O-β-D-glucosyl[1–4]-α-D-glucoside. The literature survey reveals that most of the pharmacological investigations on S. cordifolia are limited to crude plant extracts and few isolated pure compounds. Therefore, there is a need to evaluate many other unexplored bioactive phytoconstituents with evidences so as to justify the traditional usages of S. cordifolia. Furthermore, detailed studies on the action of mechanisms of these isolated compounds supported by clinical research are necessary for validating their application in contemporary medicines. The aim of the present chapter is to provide a detailed information on the ethnobotanical, phytochemical, and pharmacological aspects of S. cordifolia

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Pollutant concentrations and exposure variability in four urban microenvironments of London

We compared various pollutant concentrations (PM1, PM2.5, PM10, PNC, BC) at four different urban microenvironments (MEs) in London (Indoor, IN; Traffic Intersection, TI; Park, PK; and Street Canyon, SC). The physico-chemical characteristics of particles were analysed, and the respiratory deposition doses (RDD) were estimated. Field measurements were conducted over a period of 121 days. The mean PM2.5 (PNC) concentrations were found to be 9.47 ± 7.05 (16366 ± 11815), 8.09 ± 4.57 (10951 ± 6445), 5.11 ± 2.96 (7717 ± 4576), 3.88 ± 3.06 (5672 ± 2934) μg m−3 (# cm−3) at TI, SC, PK and IN, respectively. PM2.5, PM10 and PNC exhibited a trend of TI \u3e SC \u3e PK \u3e IN; higher concentrations for PM1 and BC were observed at IN than PK due to the emissions from printers, producing a trend of TI \u3e SC \u3e IN \u3e PK. We observed 12%–30% higher fine PM concentrations at TI and SC sites during morning peak (07:00–09:30) than the evening peak hours (16:00–19:00); while IN showed a smaller variation in fine PM concentrations compared with outdoor TI, PK and SC sites owing to their prevalence in the IN for a longer time. Fine and ultrafine PM containing potentially toxic trace transition metals including Fe, Ti, Cr, Mn, Al and Mg were detected by high resolution electron microscopy at all sites. There was a similar relative abundance of different elements at the TI, IN and PK sites, which suggests a transport of PM between MEs. RDD for PM1 was highest (2.45 ± 2.27 μg h−1) at TI for females during running; PM2.5 and PM10 were highest at SC (11.23 ± 6.34 and 37.17 ± 20.82 μg h−1, respectively). The results show that the RDD variation between MEs does not follow the PM concentration trend. RDD at PK was found to be 39%–53% lower than TI and SC during running for all the PM fractions. Overall, the study findings show the air quality variation at different MEs and reveals the exposure inequalities around the city, which enable the management of personal exposure by selecting appropriate MEs for different activities

Corrigendum to “Pollutant concentrations and exposure variability in four urban microenvironments of London” [Atmos. Environ. 298 (2023) 119624](S135223102300050X)(10.1016/j.atmosenv.2023.119624)

The authors regret to inform the missing name from the co-authors list and apologise for any inconvenience caused. The new authors’ list should read as: Mamatha Tomsona,e, Prashant Kumara,b,c,d, Gopinath Kalaiarasana, Juan C. Zavala-Reyesa, f, Marta Chiapascoh, Mark A. Sephtong, Gloria Youngh, Alexandra E. Porterh, Michał M. KłosowskiiaGlobal Centre for Clean Air Research (GCARE), School of Sustainability, Civil and Environmental Engineering, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, United Kingdom bInstitute for Sustainability, University of Surrey, Guildford, GU2 7XH, Surrey, United Kingdom cDepartment of Civil, Structural & Environmental Engineering, Trinity College Dublin, Dublin, Ireland dSchool of Architecture, Southeast University, Nanjing, China eSMART Infrastructure Facility, Faculty of Engineering and Information Science, University of Wollongong, Wollongong, 2522, NSW, Australia fEscuela Nacional de Estudios Superiores–Mérida, Universidad Nacional Autónoma de México, 97357, Mérida, Yucatán, México gDepartment of Earth Science and Engineering, Prince Consort Road, Imperial College London, SW72AZ, United Kingdom hDepartment of Materials, Prince Consort Road, Imperial College London, SW72AZ, United Kingdom iResearch Complex at Harwell, Harwell Campus R92, OX11 0FA, United Kingdom The updated CRediT authorship contribution statement should read as: Mamatha Tomson: Conceptualization, Writing – original draft, Methodology, Validation, Visualization, Writing – review & editing. Prashant Kumar: Conceptualization, Investigation, Methodology, Project administration, Resources, Supervision, Visualization, Writing – original draft, Writing – review & editing. Gopinath Kalaiarasan: Writing – review & editing. Juan C. Zavala-Reyes: Writing – review & editing. Marta Chiapasco: Writing – review & editing. Mark A. Sephton: Writing – review & editing. Gloria Young: Writing – review & editing. Alexandra E. Porter: Writing – review & editing, Funding acquisition. Michał M. Kłosowski: Investigation and Formal analysis (Section 3.5)

Active Air Monitoring for Understanding the Ventilation and Infection Risks of SARS-CoV-2 Transmission in Public Indoor Spaces

Indoor, airborne, transmission of SARS-CoV-2 is a key infection route. We monitored fourteen different indoor spaces in order to assess the risk of SARS-CoV-2 transmission. PM2.5 and CO2 concentrations were simultaneously monitored in order to understand aerosol exposure and ventilation conditions. Average PM2.5 concentrations were highest in the underground station (261 ± 62.8 μgm−3), followed by outpatient and emergency rooms in hospitals located near major arterial roads (38.6 ± 20.4 μgm−3), the respiratory wards, medical day units and intensive care units recorded concentrations in the range of 5.9 to 1.1 μgm−3. Mean CO2 levels across all sites did not exceed 1000 ppm, the respiratory ward (788 ± 61 ppm) and the pub (bar) (744 ± 136 ppm) due to high occupancy. The estimated air change rates implied that there is sufficient ventilation in these spaces to manage increased levels of occupancy. The infection probability in the medical day unit of hospital 3, was 1.6-times and 2.2-times higher than the emergency and outpatient waiting rooms in hospitals 4 and 5, respectively. The temperature and relative humidity recorded at most sites was below 27 °C, and 40% and, in sites with high footfall and limited air exchange, such as the hospital medical day unit, indicate a high risk of airborne SARS-CoV-2 transmission

Active Air Monitoring for Understanding the Ventilation and Infection Risks of SARS-CoV-2 Transmission in Public Indoor Spaces

Peer reviewed: TrueFunder: Leverhulme TrustIndoor, airborne, transmission of SARS-CoV-2 is a key infection route. We monitored fourteen different indoor spaces in order to assess the risk of SARS-CoV-2 transmission. PM2.5 and CO2 concentrations were simultaneously monitored in order to understand aerosol exposure and ventilation conditions. Average PM2.5 concentrations were highest in the underground station (261 ± 62.8 μgm−3), followed by outpatient and emergency rooms in hospitals located near major arterial roads (38.6 ± 20.4 μgm−3), the respiratory wards, medical day units and intensive care units recorded concentrations in the range of 5.9 to 1.1 μgm−3. Mean CO2 levels across all sites did not exceed 1000 ppm, the respiratory ward (788 ± 61 ppm) and the pub (bar) (744 ± 136 ppm) due to high occupancy. The estimated air change rates implied that there is sufficient ventilation in these spaces to manage increased levels of occupancy. The infection probability in the medical day unit of hospital 3, was 1.6-times and 2.2-times higher than the emergency and outpatient waiting rooms in hospitals 4 and 5, respectively. The temperature and relative humidity recorded at most sites was below 27 °C, and 40% and, in sites with high footfall and limited air exchange, such as the hospital medical day unit, indicate a high risk of airborne SARS-CoV-2 transmission.</jats:p