Resveratrol attenuates staphylococcal enterotoxin B-activated immune cell metabolism via upregulation of miR-100 and suppression of mTOR signaling pathway

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq) unveiled the decreased expression of mTOR in a variety of immune cells in the lungs. There was also an increase in glycolytic and mitochondrial respiration in the cells from SEB + VEH group in comparison with SEB + RES group. Together these data suggested that RES alters the metabolic reprogramming of SEB-activated immune cells, through suppression of mTOR activation and its down- and upstream effects on energy metabolism. Also, miR-100 could serve as novel potential therapeutic molecule in the amelioration of ARDS.

Microbiological profile and their antibiogram of bloodstream infections amongst first and second surge of the COVID-19 patients in a tertiary care hospital.

Introduction: The world is experiencing a pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. The prescription of a superfluity of unnecessary antibiotics without regard for the potential for increased antimicrobial resistances is extensive and unimpeded during the COVID-19 pandemic. Aims: To compare the microorganisms and the pattern of antimicrobial resistance of bacteremia during the first and second waves of the COVID-19 pandemic in a tertiary care hospital. Methods and Material: This retrospective observational study, to compared the blood culture of the COVID-19 pandemic during the first wave (April 2020 to September 2020) and the second wave (April 2021 to September 2021). All the blood culture isolates were identified and the antimicrobial susceptibility testing was done according to standard guidelines. Results: Out of 1470 blood culture samples, 259 (17.6%) blood bacterial isolates were grown in the first wave and, out of 4200 blood culture samples, 711 (16.9%) bacterial isolated during the second wave of the COVID-19 pandemic. Coagulase-negative staphylococcus (CONS) was 32.8% followed by Staphylococcus aureus 29.7% in COVID first wave and staphylococcus aureus (48.9%) followed by Klebsiella pneumoniae (11.6%) during COVID second wave were the most prevalent isolates. Conclusions: This study shows that coagulase-negative staphylococcus aureus and multidrug-resistant Klebsiella spp. are the leading causes of bloodstream coagulase-negative infections during both the first and second wave in the bloodstream COVID-19 pandemic.

Review on distribution, fate, and management of potentially toxic elements in incinerated medical wastes.

Medical wastes include all solid and liquid wastes that are produced during the treatment, diagnosis, and immunisation of animals and humans. A significant proportion of medical waste is infectious, hazardous, radioactive, and contains potentially toxic elements (PTEs) (i.e., heavy metal (loids)). PTEs, including arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg), are mostly present in plastic, syringes, rubber, adhesive plaster, battery wastes of medical facilities in elemental form, as well as oxides, chlorides, and sulfates. Incineration and sterilisation are the most common technologies adopted for the safe management and disposal of medical wastes, which are primarily aimed at eliminating deadly pathogens. The ash materials derived from the incineration of hazardous medical wastes are generally disposed of in landfills after the solidification/stabilisation (S/S) process. In contrast, the ash materials derived from nonhazardous wastes are applied to the soil as a source of nutrients and soil amendment. The release of PTEs from medical waste ash material from landfill sites and soil application can result in ecotoxicity. The present study is a review paper that aims to critically review the dynamisms of PTEs in various environmental media after medical waste disposal, the environmental and health implications of their poor management, and the common misconceptions regarding medical waste.

Resveratrol attenuates staphylococcal enterotoxin B-activated immune cell metabolism via upregulation of miR-100 and suppression of mTOR signaling pathway.

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq) unveiled the decreased expression of mTOR in a variety of immune cells in the lungs. There was also an increase in glycolytic and mitochondrial respiration in the cells from SEB + VEH group in comparison with SEB + RES group. Together these data suggested that RES alters the metabolic reprogramming of SEB-activated immune cells, through suppression of mTOR activation and its down- and upstream effects on energy metabolism. Also, miR-100 could serve as novel potential therapeutic molecule in the amelioration of ARDS.

Development and implementation of a sustainable COVID-19 training package for healthcare workers: Experience from a teaching hospital of North India.

Background: With the impending threat of future COVID-19 waves, it is imperative that teaching hospitals develop, implement, and evaluate a systematic training program to render HCW elastic in delivering COVID-19 related services. We present our experience in developing, implementing, and evaluating a sustainable and scalable COVID-19 patient management training package for healthcare workers. Materials and Methods: A mixed-methods study design was used. Rapid assessment to understand the need of the trainees and identify the available resources was done followed by planning of the training module and its implementation. The program was evaluated for effectiveness and sustainability. Data analysis was done using descriptive statistics and qualitative data generated from open-ended questions in the feedback forms and the discussions were analyzed using rapid content analysis. Results: A total of 66.8% of the doctors and 18.9% of the nurses were trained by online synchronous mode while 55.0% of the nursing officers and 47.1% of the nursing orderlies and paramedical staff were trained in onsite skill development sessions. Need assessment identified that healthcare workers were ill-prepared to use medical devices such as Bipap machines, ventilators, and oxygen delivery devices. The participants mentioned that the multidisciplinary approach and video-based demonstrations facilitated their online learning while the incremental learning approach, easy-to-understand terminology and hands-on experience facilitated their onsite skill development sessions. Conclusion: The COVID-19 training package developed was multidisciplinary, effective, sustainable, and scalable in a resource-limited setting. We suggest that this model can be adapted by healthcare organizations to develop and implement such training packages for their healthcare workers.

Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis.

Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.

Intertidal Zone Effects on Occurrence, Fate and Potential Risks of Microplastics with Perspectives under COVID-19 Pandemic

Micro-(nano-)plastics have become emerging contaminants worldwide in recent years. However, there has not been a critical review on their fate and potential risk in intertidal zones with different geological conditions. Thus, this review provides a comprehensive analysis of the roles of intertidal zones in accumulation or transportation of microplastics, involving convergence, migration, plastiglomerate, and ingestion effects. It is found that microplastics (MPs) are likely to be stranded in mudflats but be transported across the sandy beaches according to their intrinsic and external conditions. Meanwhile, MPs could also form the contamination of plastiglomerate and act as vectors for contaminants, even pathogens, in rocky and biological beaches. Thus, MPs together with nanoplastics (NPs) could potentially threaten the ecosystems of the intertidal zone by their ingestion and translocation. In view of the upsurge of personal protective equipment (PPE) during COVID-19, the occurrence of discarded PPE in the intertidal zones has also been summarized and discussed. Despite that the amount of discarded PPE is relatively smaller than other MPs, the pollution caused by these wastes could increase the possibility for pathogen-attached MPs becoming the source for spreading disease among wildlife and humans. It will be of vital importance for understanding the roles of intertidal zone in influencing the fate and ecotoxicity of the MPs. Moreover, the in-depth discussion on fate of the PPE in each kinds of intertidal zones can be conducive to drawing more attentions on plastic concerns in COVID-19 pandemic and achieving environmental sustainability.

Psychological impact of COVID-19 on Mental Health Professionals working in different tertiary level healthcare setups of India

Background: The exponential increase of mental health issues associated with COVID-19 increased the pressure on mental health professionals. Hence, this study was conducted to assess the psychological consequences of Covid-19 on mental health professionals working in the country. Methods: This multi-centric study was conducted on mental health professionals of the country. The data collection was done online by using a survey form created through the Google Forms platform. Socio-demographic data sheet, Coronavirus Anxiety Scale and Depression, Anxiety and Stress Scale - 21 Items (DASS-21) were used for data collection. The data analysis was done by using Statistical Package of Social Sciences (SPSS) Windows version 25. Descriptive statistics, Independent Samples t Test and Pearson's Correlation (Two Tailed) were used for data analysis. Results: The mean age of the selected mental health professionals was noted to be 33.89 ± 7.79 years. In all the domains of the Depression, Anxiety and Stress Scale - 21 Items (DASS-21) females scored significantly higher than males (p =0.0001). The psychiatric nurses reported significantly higher level of anxiety and stress in the DASS-21 items. Significant positive correlations were noted between the corona virus anxiety and the three domains of the DASS-21. Conclusion: A considerable psychological impact of the Covid-19 pandemic was observed on the mental health professionals of our country. Increased anxiety about the corona virus was associated with increased likelihood of depression, stress and anxiety among the mental health professionals.

Resveratrol-mediated attenuation of superantigen-driven acute respiratory distress syndrome is mediated by microbiota in the lungs and gut.

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of agents, including Staphylococcal Enterotoxin B (SEB). Interestingly, a significant proportion of patients with COVID-19, also develop ARDS. In the absence of effective treatments, ARDS results in almost 40% mortality. Previous studies from our laboratory demonstrated that resveratrol (RES), a stilbenoid, with potent anti-inflammatory properties can attenuate SEB-induced ARDS. In the current study, we investigated the role of RES-induced alterations in the gut and lung microbiota in the regulation of ARDS. Our studies revealed that SEB administration induced inflammatory cytokines, ARDS, and 100% mortality in C3H/HeJ mice. Additionally, SEB caused a significant increase in pathogenic Proteobacteria phylum and Propionibacterium acnes species in the lungs. In contrast, RES treatment attenuated SEB-mediated ARDS and mortality in mice, and significantly increased probiotic Actinobacteria phylum, Tenericutes phylum, and Lactobacillus reuteri species in both the colon and lungs. Colonic Microbiota Transplantation (CMT) from SEB-injected mice that were treated with RES as well as the transfer of L. reuteri into recipient mice inhibited the production of SEB-mediated induction of pro-inflammatory cytokines such as IFN-γ and IL-17 but increased that of anti-inflammatory IL-10. Additionally, such CMT and L. reuteri recipient mice exposed to SEB, showed a decrease in lung-infiltrating mononuclear cells, cytotoxic CD8+ T cells, NKT cells, Th1 cells, and Th17 cells, but an increase in the population of regulatory T cells (Tregs) and Th3 cells, and increase in the survival of mice from SEB-mediated ARDS. Together, the current study demonstrates that ARDS induced by SEB triggers dysbiosis in the lungs and gut and that attenuation of ARDS by RES may be mediated, at least in part, by alterations in microbiota in the lungs and the gut, especially through the induction of beneficial bacteria such as L. reuteri.

Δ9-Tetrahydrocannabinol Prevents Mortality from Acute Respiratory Distress Syndrome through the Induction of Apoptosis in Immune Cells, Leading to Cytokine Storm Suppression.

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.

PM2.5 diminution and haze events over Delhi during the COVID-19 lockdown period: an interplay between the baseline pollution and meteorology.

Delhi, a tropical Indian megacity, experiences one of the most severe air pollution in the world, linked with diverse anthropogenic and biomass burning emissions. First phase of COVID-19 lockdown in India, implemented during 25 March to 14 April 2020 resulted in a dramatic near-zeroing of various activities (e.g. traffic, industries, constructions), except the "essential services". Here, we analysed variations in the fine particulate matter (PM2.5) over the Delhi-National Capital Region. Measurements revealed large reductions (by 40-70%) in PM2.5 during the first week of lockdown (25-31 March 2020) as compared to the pre-lockdown conditions. However, O3 pollution remained high during the lockdown due to non-linear chemistry and dynamics under low aerosol loading. Notably, events of enhanced PM2.5 levels (300-400 µg m-3) were observed during night and early morning hours in the first week of April after air temperatures fell close to the dew-point (~ 15-17 °C). A haze formation mechanism is suggested through uplifting of fine particles, which is reinforced by condensation of moisture following the sunrise. The study highlights a highly complex interplay between the baseline pollution and meteorology leading to counter intuitive enhancements in pollution, besides an overall improvement in air quality during the COVID-19 lockdown in this part of the world.

COVID-19 waste management: Effective and successful measures in Wuhan, China.

•Medical wastes will drastically increase due to Covid-19-outbreak.•Safe and sustainable waste management is a major concern.•Experience and lessons can be learned for medical waste management in China.