Biology subjects

Ramachandran, G.

Publications and source records attributed to Ramachandran, G..

5 recordsLinked to original sources

bioRxiv2025

Inactivation of Airborne Pathogen Surrogates by Triethylene Glycol

The COVID-19 outbreak brought to the fore the importance of airborne transmission in spreading human infectious diseases and highlighted the need for sustainable mitigation strategies. Triethylene glycol (TEG) has been documented as having microbicidal capabilities and has been proposed as one such mitigation strategy. Aerosolized TEG exhibits antimicrobial activity against airborne microorganisms; Grignard Pure Technology was developed to safely aerosolize TEG for decontamination of enclosed spaces. Here we show that this TEG formulation effectively inactivates airborne microorganisms, resulting in 2 to 4.5 net log reduction in concentration of viable bacteria, viruses, and mycobacteria within 30-60 minutes at TEG concentration (aerosol + vapor) of [~]0.7 mg/m3, which is well within the range considered safe for humans. Our data also demonstrate that aerosolizing both the test organisms and the antimicrobial product provides a more accurate and relevant measure of the products efficacy for indoor usage than traditional surface - or solution - based disinfection assays. Accurate evaluation of antimicrobial efficacy is a crucial step in adopting novel interventions and tools to control airborne pathogens that pose a public health risk. Our findings argue that testing protocols must match the intended use of any intervention. Given the safety concerns of aerosolizing human pathogens for direct testing of airborne infectious burden, we also advance an approach for selecting suitable surrogate microorganisms based on their phenotypic and biophysical similarity to corresponding pathogenic species. ImportanceDuring the COVID-19 pandemic, personal protective equipment, social distancing, and even vaccinations proved sub-optimal in controlling the spread of COVID-19. Public health practice and the hierarchy of controls emphasize primary prevention, whereby the pathogen is removed or destroyed before exposure to the public. Triethylene glycol (TEG) has the potential to inactivate airborne pathogens and limit their spread. TEG is designated a "safer chemical" by the US EPA and has been used for decades in aerosol deodorizers and theatrical special effects. This study shows that aerosolized TEG is highly effective at eliminating a wide spectrum of viable airborne pathogen surrogates at concentrations well below the threshold of safety concern. Thus, it may afford significant protection against the transmission of infectious agents with pandemic potential.

microbiology↗

bioRxiv2023

Subchronic exposure to ambient PM2.5 impairs novelty recognition and spatial memory

Air pollution remains a great challenge for public health, with the detrimental effects of air pollution on cardiovascular, rhinosinusitis, and pulmonary health increasingly well understood. Recent epidemiological associations point to the adverse effects of air pollution on cognitive decline and neurodegenerative diseases. Mouse models of subchronic exposure to PM2.5 (ambient air particulate matter < 2.5 {micro}m) provide an opportunity to demonstrate the causality of target diseases. Here, we subchronically exposed mice to concentrated ambient PM2.5 for 7 weeks (5 days/week; 8h/day) and assessed its effect on behavior using standard tests measuring cognition or anxiety-like behaviors. Average daily PM2.5 concentration was 200 {micro}g/m3 in the PM2.5 group and 10 {micro}g/m3 in the filtered air group. The novel object recognition (NOR) test was used to assess the effect of PM2.5 exposure on recognition memory. The increase in exploration time for a novel object versus a familiarized object was lower for PM2.5-exposed mice (42% increase) compared to the filtered air (FA) control group (110% increase). In addition, the calculated discrimination index for novel object recognition was significantly higher in FA mice (67 %) compared to PM2.5 exposed mice (57.3%). The object location test (OLT) was used to examine the effect of PM2.5 exposure on spatial memory. In contrast to the FA-exposed control mice, the PM2.5 exposed mice exhibited no significant increase in their exploration time between novel location versus familiarized location indicating their deficit in spatial memory. Furthermore, the discrimination index for novel location was significantly higher in FA mice (62.6%) compared to PM2.5 exposed mice (51%). Overall, our results demonstrate that subchronic exposure to higher levels of PM2.5 in mice causes impairment of novelty recognition and spatial memory.

pharmacology and toxicology↗

bioRxiv2023

Optineurin is involved in regulating macrophage responses during mycobacterial infection

Autophagy has emerged as a critical innate immune mechanism for host elimination of intracellular pathogens, however, the role of the autophagy receptor optineurin during mycobacterial infection is not fully understood. To address this lacuna, we infected bone marrow-derived macrophages (BMDMs) derived from Optn+/+ and Optn-/- mice with Mycobacterium smegmatis, and observed the infection outcome at sequential time points. While low multiplicity of infection (MOI) did not show any significant difference between BMDMs from the two groups, at high MOI Optn-/- mice-derived macrophages showed significantly lower colony forming unit counts, as well as lower cell counts at 12 h and 24 h post-infection. Quantification of cell numbers and nuclear morphologies at various time points post-infection indicated a markedly higher cell death in the optineurin-deficient macrophages. Optineurin-deficient macrophages showed significantly lower levels of the autophagosomal protein LC3-II upon infection, indicating a potential role for optineurin in regulating autophagy during mycobacterial infection. Moreover, when stimulated by bacterial LPS, optineurin deficient macrophages, showed altered levels of the inflammatory cytokine pro-IL-1{beta}. These observations taken together suggest a novel regulatory role for optineurin during mycobacterial infection, with its deficiency leading to an impairment in macrophage responses.

cell biology↗

bioRxiv2022

The efficiency of Grignard Pure™ to inactivate airborne SARS-CoV-2 surrogate

Grignard Pure (GP) is a unique and proprietary blend of Triethylene Glycol (TEG) and inert ingredients designed for continuous antimicrobial treatment of air. GP received approval from the US EPA under its Section 18 Public Health Emergency Exemption program for use in seven states. This study characterizes the efficacy of GP for inactivating MS2 bacteriophage - a non-enveloped virus widely used as a surrogate for SARs-CoV-2. Experiments measured the decrease in the airborne viable MS2 concentration in the presence of different concentrations of GP from 60 to 90 minutes, accounting for both natural die-off and settling of MS2. Experiments were conducted both by introducing GP aerosol into air containing MS2 and by introducing airborne MS2 into air containing GP aerosol. GP is consistently able to rapidly reduce viable MS2 bacteriophage concentration by 2-3 logs at GP concentrations of 0.02 mg/m3 to 0.5 mg/m3 (corresponding to TEG concentrations of 0.012 mg/m3 to 0.287 mg/m3). Related GP efficacy experiments by the US EPA, as well as GP (TEG) safety and toxicology, are also discussed. SynopsisLimited research on the germicidal properties of triethylene glycol against airborne pathogens was conducted during the 1940s and 50s. This paper investigates the inactivation rate of airborne bacteriophage MS2 by Grignard Pure product, containing a unique and proprietary blend of Triethylene Glycol (TEG) and inert ingredients.

microbiology↗

bioRxiv2018

Real-time fine aerosol exposures in taconite mining operations

Respiratory health effects such as mesothelioma, silicosis, and lung cancer have been shown to be associated with working in the taconite mining industry. Taconite workers may also have elevated risks from cardiovascular disease (CVD), although the relationship of CVD to dust exposures at these mines has not been well-studied. Motivated by evidence from environmental epidemiological studies and occupational cohorts that have implicated the effects of fine particulates with increased risk of cardiovascular diseases, we conducted an air monitoring campaign to characterize fine aerosol concentrations at 91 locations across six taconite mines using an array of direct-reading instruments to obtain measurements of mass concentrations (PM2.5 or particles with aerodynamic diameter less than 2.5 m, and respirable particulate matter or RPM), alveolar-deposited surface area concentrations (ADSA), particle number concentrations (PN), and particle size distributions. To analyze these data, we fit a Bayesian hierarchical model with an AR(1) correlation structure to estimate exposure while accounting for temporal correlation. The highest estimated geometric means (GMs) were observed in the pelletizing and concentrating departments (pelletizing maintenance, balling drum operator, and concentrator operator) for PM2.5 and RPM. ADSA and PN generally had highest GMs in the pelletizing department, which processed large amounts of powder-like particles into iron pellets. The within-location variability (GSD_WL) generally ranged from 1 to 3 for all exposure metrics, except for a few locations which indicated changes of activities that caused the exposures to change. Between-location variability (GSD_BL) estimates were generally higher than GSD_WL, indicating larger differences in exposure levels at different locations between mines than at individual locations over the course of several hours. Ranking between PM2.5 and RPM generally agree with each other, whereas ADSA and PN were more consistent with each other, with some overlap with PM2.5 and RPM. Differences in ranking these groups may have potential implication for occupational epidemiological studies that rely on exposure information to detect an exposure-response relationship for various job groups. Future epidemiological studies investigating fine aerosol exposures and health risks in occupational settings are encouraged to use multiple metrics to see how they influence health outcomes risk.

epidemiology↗