Nanocarrier - Mediated Salinomycin Delivery Induces Apoptosis and Alters EMT Phenomenon in Prostate Adenocarcinoma.

Salinomycin (Sal) has been recently discovered as a novel chemotherapeutic agent against various cancers including prostate cancer which is one of the most commonly diagnosed cancers affecting male populations worldwide. Herein we designed salinomycin nanocarrier (Sal-NPs) to extend its systemic circulation and to increase its anticancer potential. Prepared nanoform showed high encapsulation and sustained release profile for salinomycin. The present study elucidated the cytotoxicity and mechanism of apoptotic cell death of Sal-NPs against prostate cancer both in vitro and in vivo. At all measured concentrations, Sal-NPs showed more significant cytotoxicity to DU145 and PC3 cells than Sal alone. This effect was mediated by apoptosis, as confirmed by ROS generation, loss of MMP and cell cycle arrest at the G1 phase in both cells. Sal-NPs efficiently inhibited migration of PC3 and DU145 cells via effectively downregulating the epithelial mesenchymal transition. Also, the results confirmed that Sal-NPs can effectively inhibit the induction of Prostate adenocarcinoma in male Wistar rats. Sal-NPs treatment exhibited a decrease in tumour sizes, a reduction in prostate weight, and an increase in body weight, which suggests that Sal-NPs is more effective than salinomycin alone. Our results suggest that the molecular mechanism underlying the Sal-NPs anticancer effect may lead to the development of a potential therapeutic strategy for treating prostate adenocarcinoma.

To Study the Distress, Anxiety, Depression, and Sleep Effects of the COVID-19 Pandemic on Essential Workers.

Essential care workers like police personnel, social workers, and office and administrative staff of health institutions are also at increased risk of coronavirus disease 2019 (COVID-19) exposure along with healthcare workers. The present study aims to estimate the distress, anxiety, depression, and sleep impact of COVID-19 pandemic on essential workers through an online survey. This cross-sectional study (included 369 participants) was conducted in Chandigarh through an online survey using three psychological scales: Peritraumatic Distress Inventory (PDI), Insomnia Severity Index, and Depression Anxiety Stress Scale. Three-hundred-sixty-nine frontline warriors from hospital and community settings were included in the study. The respondents include police personnel (274; 73.66%), office staff (24; 6.45%), social workers (53; 14.24%), and media staff (21; 5.65%). Maximum distress was reported by media/transport officials on duty (85.7%). The majority of them scored high (>14), and slightly less than one-fourth (23.8%) scored significantly abnormal (>23) on PDI. About 42.9% reported moderate insomnia, 52.4% exhibited severe anxiety, and 33.3% of media/transport participants reported severe depression. Psychological morbidity is high in media/transport and social workers working in the community during the COVID-19 pandemic.

Alcohol induces ER stress and apoptosis by inducing oxidative stress and disruption of calcium homeostasis in glial cells.

Alcohol has teratogenic effects that can cause developmental abnormalities and alter anatomical and functional characteristics of the developed brain and other organs. Glial cells play a crucial role in alcohol metabolism and protect neurons from toxic effects of alcohol. However, chronic alcohol exposure can lead to uncontrollable levels of reactive oxygen species, resulting in the death of glial cells and exposing neuronal cells to the toxic effects of alcohol. The exact molecular mechanism of alcohol-induced glial cell death has not been fully explored. This study reported that different concentrations of alcohol induce different expressions of ER stress markers in glial cells, focusing on the role of endoplasmic reticulum (ER) stress. Alcohol-induced concentration-dependent toxicity in both cells also induced oxidative stress, leading to mitochondrial damage. The expression of p53 and apoptotic proteins was significantly up-regulated after alcohol exposure, while Bcl2 (anti-apoptotic) was down-regulated. The signalling pathway for ER stress was activated and up-regulated marker proteins in a concentration-dependent manner. Cells pre-treated with BAPTA-AM and NAC showed significant resistance against alcohol assault compared to other cells. These in vitro findings will prove valuable for defining the mechanism by which alcohol modulates oxidative stress, mitochondrial and ER damage leading to glial cell death.

Active surveillance of adverse events following COVID-19 vaccines in a tertiary care hospital.

Background: Vaccination is a safe and effective way to prevent disease and save lives, but it may also produce some undesirable adverse events (AEs)which may affect healthy individuals. Therefore, the monitoring of AE following immunization (AEFIs) is necessary. The objective of this study was to assess the AEs following COVID-19 vaccinations in a tertiary care hospital. Methodology: The study was conducted as active vaccine safety surveillance for a period of 6 months among the COVID-19 vaccine beneficiaries of the study site. Active surveillance was conducted via initiating two telephone contacts. The first surveillance was conducted in 8 days and the second surveillance after 28 days of post-vaccination. All identified AEs following immunizations (AEFIs) were reported and analysed by the AEFI investigation team at the study site. The causality assessment of each identified AEFI was performed using the World Health Organization's causality assessment algorithm. Results: A total of 2927 enrolled study population completed the study with a response rate of 80.85%. The study identified 902 AEFIs from 614 study populations with an incidence rate of 20.97%. Of which 794 and 79 AEFIs were associated with COVISHIELD™ and COVAXIN®, respectively. The majority of the events were reported among the age group of 18-29 years. Overall, only three events were serious and no deaths were reported among the study population. A total of 75.59% of events had a consistent causal association with vaccination and were categorized as vaccine product-related reactions. The study identified various factors such as gender (p = 0.019), age (p < 0.05), co-morbid status (p = 0.032) and dose number (p = 0.001) as potential predictors for development of AEFI. Conclusion: The study identified only 0.33% of events as serious, and 99.67% of the study population recovered from the AEFIs, which reveals that COVISHIELD™ and COVAXIN® have a generally favourable safety profile. However, close monitoring is required to identify the potential signals, as the safety data from the clinical trials are limited.

Limb Salvage Surgery in an Enormously Large Pelvic Malignant Bone Tumor.

Introduction: Malignant transformation of pelvic osteochondroma is a rare entity. Large size and late presentation impose threat to life as well as limb. We report a case of limb salvage surgery in an enormously large secondary chondrosarcoma arising from pelvic bone. Case Report: A 60-year-old male presented with a colossal swelling at groin reaching up to distal thigh. He was walking with a wide-based gait due to pain and discomfort. 30 year back, the patient first reported this swelling of pea size, for which he was advised surgery but due to fear of surgery and economic reason he refused. Swelling gradually increased in size and reached up to distal thigh in the past 30 years. It was hard and non-tender up to 6 months back, when suddenly a change in consistency from hard to soft in distal area was noticed. On examination, a large soft cystic swelling was hanging from his pubic area. Tumor was fixed at base on proximal end. On magnetic resonance imaging, size of tumor was 281 mm in length, 263 mm in width, and 250 mm in anteroposterior diameter. Tumor was arising from superior and ischiopubic rami. However, no intra-articular extension was seen. A radiographic skeletal survey and bone scan did not reveal any other lesion. On biopsy, chondrogenic tumor composed of lobules of chondroid material with no cellular atypia or evidence of malignancy was reported. Considering the age of patient, rapid progression in recent months, size and duration of tumor, and type 3 pelvic resection was planned. Using utilitarian pelvic incision with perineal extension, separating long adductor muscles and deep femoral artery tumor, tumor excised with osteotomy at pubic symphysis, and on superior and inferior pubic rami. With minor wound complications, wound healed in 3 weeks. Post-operative biopsy reported as Grade 1 chondrosarcoma. At 3-year follow-up, the patient has no complains and no sign of recurrence noticed. Conclusion: Limb salvage surgery is a suitable option even in enormously large musculoskeletal malignancy. Proper counseling and tracking of patients are must to avoid future complications.

Coronary Ostial Acquired Occlusion or Congenital Atresia: An Ongoing Discussion.

Coronary ostial atresia is a developmental abnormality that typically causes asymptomatic anomalies in the coronary blood supply. This case report, which presents 2 symptomatic patients with right coronary artery abnormalities, explores difficulties in diagnosing coronary ostial atresia and distinguishing it from single coronary artery and coronary artery disease-related acquired occlusion. Factors underlying management decisions are also discussed.

Mental health of health care workers during the hour of crisis - A study from tertiary care hospital in North India.

Background and Aims: This cross-sectional study aimed to analyze the psychosocial, behavioral, and sleep impact of coronavirus disease-19 (COVID-19) pandemic on healthcare workers (HCWs) at a tertiary-care hospital in Northern India. Materials and Methods: An online questionnaire including three psychological scales - peritraumatic distress inventory (PDI), insomnia Severity Index (ISI), and Depression anxiety stress scale was circulated among the HCWs at a tertiary-care hospital in Northern India. Results: Three hundred and ninety-six HCWs (Mean age standard deviation: 34.8 [8.1%] years; 181 females) responded. Place of posting was active COVID area (27.2%), reserve active COVID team (23.2%), trained reserve pool (29.5%), and non-COVID areas (19.9%). More than half of all the respondents (51%) had abnormal PDI score (>14) with a propensity to develop posttraumatic stress disorder. Furthermore, there was a significantly higher prevalence of abnormal PDI scores in those involved in active COVID care units (74%) versus non-COVID care unit (24%, P = 0.001). More than 60% of all the respondents had abnormal ISI score suggesting significant insomnia. Stress was seen in 71% of all the respondents while 82% were anxious and 77% participants had depressive symptoms. Hence, the psychological morbidity among the HCWs was high. Conclusion: Our study found a much higher prevalence of peritraumatic distress, insomnia, anxiety, stress, and depression among the HCWs, more so in those working in COVID areas. Factors indigenous to Indian population in terms of psychological health must be studied and addressed to reduce this psychological morbidity since the battle with COVID is long.

Biological Stabilisation vs Mechanical Fixation: Do We Always Require Instrumentation in Anterior Decompression Surgeries for Thoracolumbar Spinal Tuberculosis?

Study Design: A retrospective cohort study. Purpose: To compare the outcomes of anterior decompression with bone grafting alone and anterior decompression with bone grafting and fixation. Methods: 93 patients with minimum 2 year follow-up were included in the study. 50 patients had undergone anterior decompression with bone grafting without instrumentation (group 1) and 43 patients with instrumentation (group 2). Both groups were compared using their demographic data, vertebral level of involvement, neurological recovery and progression of kyphotic deformity. Results: Demographic data and pre-operative parameters were comparable in both groups. The mean (SD) of pre-operative kyphotic angle (in degrees) in group 1 was 29° (8.47°) and in group 2 was 29.81° (9.51°). The mean loss of correction at follow-up was 9.6° for group 1 compared to 3.4° for group 2. The mean loss of correction in patients of group 1 involving upper thoracic spine was 5.6°. There was no significant difference between the two groups across different age groups. Conclusion: Use of anterior instrumentation for decompression surgeries in cases of tubercular spine have shown significantly better results compared to strut grafting alone with respect to restricting the progression of kyphotic deformity at follow-up. Instrumentation may be avoided in patients older than 60 years of age and those involving the upper thoracic spine, more so if both of these co-exist. However, further studies are needed to make our patient selection more rational, so as to avoid the failures and complications of this morbid procedure. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-023-00827-4.

Mitochondrial dysfunction and oxidative stress: Role in chronic kidney disease.

Chronic kidney disease (CKD) is associated with a variety of distinct disease processes that permanently change the function and structure of the kidney across months or years. CKD is characterized as a glomerular filtration defect or proteinuria that lasts longer than three months. In most instances, CKD leads to end-stage kidney disease (ESKD), necessitating kidney transplantation. Mitochondrial dysfunction is a typical response to damage in CKD patients. Despite the abundance of mitochondria in the kidneys, variations in mitochondrial morphological and functional characteristics have been associated with kidney inflammatory responses and injury during CKD. Despite these variations, CKD is frequently used to define some classic signs of mitochondrial dysfunction, including altered mitochondrial shape and remodeling, increased mitochondrial oxidative stress, and a marked decline in mitochondrial biogenesis and ATP generation. With a focus on the most significant developments and novel understandings of the involvement of mitochondrial remodeling in the course of CKD, this article offers a summary of the most recent advances in the sources of procured mitochondrial dysfunction in the advancement of CKD. Understanding mitochondrial biology and function is crucial for developing viable treatment options for CKD.

Prognostic Role of the Platelet-Lymphocyte Ratio in Acute Ischemic Stroke Patients Undergoing Reperfusion Therapy: A Meta-Analysis.

Background: Both inflammation and thrombotic/hemostatic mechanisms may play a role in acute ischemic stroke (AIS) pathogenesis, and a biomarker, such as the platelet-to-lymphocyte ratio (PLR), considering both mechanisms may be of clinical utility. Objectives: This meta-analysis sought to examine the effect of PLR on functional outcomes, early neurological changes, bleeding complications, mortality, and adverse outcomes in AIS patients treated with reperfusion therapy (RT). Design: Systematic Review and Meta-Analysis. Data Sources and Methods: Individual studies were retrieved from the PubMed/Medline, EMBASE and Cochrane databases. References thereof were also consulted. Data were extracted using a standardised data sheet, and systematic reviews and meta-analyses on the association of admission (pre-RT) or delayed (post-RT) PLR with defined clinical and safety outcomes were conducted. In the case of multiple delayed PLR timepoints, the timepoint closest to 24 hours was selected. Results: Eighteen studies (n=4878) were identified for the systematic review, of which 14 (n=4413) were included in the meta-analyses. PLR collected at admission was significantly negatively associated with 90-day good functional outcomes (SMD=-.32; 95% CI = -.58 to -.05; P=.020; z=-2.328), as was PLR collected at delayed timepoints (SMD=-.43; 95% CI = -.54 to -.32; P<.0001; z=-7.454). PLR at delayed timepoints was also significantly negatively associated with ENI (SMD=-.18; 95% CI = -.29 to -.08; P=.001. Conversely, the study suggested that a higher PLR at delayed timepoints may be associated with radiological bleeding and mortality. The results varied based on the type of RT administered. Conclusions: A higher PLR is associated with worse outcomes after stroke in terms of morbidity, mortality, and safety outcomes after stroke.

Role of Neutrophil-Lymphocyte Ratio in the Prognosis of Acute Ischaemic Stroke After Reperfusion Therapy: A Systematic Review and Meta-analysis.

Background: Inflammation may mediate response to acute reperfusion therapy (RT) in acute cerebral ischaemia. Neutrophil-lymphocyte ratio (NLR), an inflammatory biomarker, may play an important role in acute ischaemic stroke (AIS) prognostication. Objective: This meta-analysis sought to examine the effect of NLR on functional outcomes, mortality and adverse outcomes in AIS patients receiving RT. Methods: Individual studies were retrieved from PubMed/Medline, EMBASE and Cochrane databases. Data were extracted using a standardised data sheet and meta-analysis on association of admission (pre-RT) or delayed (post-RT) NLR with clinical/safety outcomes after RT was conducted. Results: Thirty-five studies (n = 10 308) were identified for the systematic review with 27 (n = 8537) included in the meta-analyses. Lower admission NLR was associated with good functional outcomes (GFOs), defined as 3-month modified Rankin scale (mRS) 0-2 (SMD = -.46; 95% CI = -.62 to -.29; P < .0001), mRS 0-1 (SMD = -.44; 95% CI = -.66 to -.22; P < .0001) and early neurological improvement (ENI) (SMD = -.55; 95 %CI = -.84 to -.25; P < .0001). Lower delayed admission NLR was also associated with GFOs (SMD = -.80; 95%CI = -.91 to -.68; P < .0001). Higher admission NLR was significantly associated with mortality (SMD = .49; 95%CI = .12 to .85; P = .009), intracerebral haemorrhage (ICH) (SMD = .34; 95% CI = .09 to .59; P = .007), symptomatic ICH (sICH) (SMD = .48; 95% CI = .07 to .90; P = .022) and stroke-associated infection or pneumonia (SMD = .85; 95% CI = .50, 1.19; P < .0001). Higher delayed NLR was significantly associated with sICH (SMD = 1.40; 95% CI = .60 to 2.19; P = .001), ICH (SMD = .94; 95% CI = .41 to 1.46; P < .0001) and mortality (SMD = 1.12; 95% CI = .57 to 1.67; P < .0001). There were variations in outcomes across RT groups. Conclusion: Higher admission or delayed NLR is significantly associated with worse morbidity, mortality and safety outcomes in AIS patients receiving RT.

Prevalence of paediatric hyperinflammatory conditions in paediatric and adolescent hospitalized COVID-19 patients: a systematic review and meta-analysis.

In the milieu of coronavirus disease 2019 (COVID-19), there are increasing reports of paediatric hyperinflammatory conditions (PHICs), including multisystem inflammatory syndrome in children (MIS-C), paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and Kawasaki disease (KD). Few analyses of PHIC prevalence in paediatric and adolescent hospitalized COVID-19 patients exist. The purpose of this study was to perform a meta-analysis to determine a pooled prevalence estimate of PHICs in paediatric and adolescent hospitalized patients admitted for treatment due to COVID-19. Individual studies were retrieved from PubMed/Medline, EMBASE and Cochrane databases. Relevant prevalence, baseline, treatment and outcome data were extracted using a standardized datasheet. The systematic review and meta-analysis were conducted as per the PRISMA and MOOSE guidelines. Overall, 14 studies with 2202 patients admitted for treatment due to COVID-19, among whom 780 were diagnosed with PHICs, were included. The crude estimate of prevalence was 35.42%, and the pooled estimate of prevalence was 29% (random pooled ES = 0.29; 95% CIs = 0.18-0.42; p < 0.0001; z = 7.45). A sizeable proportion of paediatric and adolescent hospitalized patients admitted for treatment due to COVID-19 are diagnosed with a PHIC warranting a high index of clinical suspicion for PHICs. Further studies are required to validate these findings.

Associations between the gut microbiome, gut microbiology and heart failure: Current understanding and future directions.

The role of the gut microbiome in pathophysiology, prognostication and clinical management of heart failure (HF) patients is of great clinical and research interest. Both preclinical and clinical studies have shown promising results, and the gut microbiome has been implicated in other cardiovascular conditions that are risk factors for HF. There is an increasing interest in the use of biological compounds produced as biomarkers for prognostication as well as exploration of therapeutic options targeting the various markers and pathways from the gut microbiome that are implicated in HF. However, study variations exist, and targeted research for individual putative biomarkers is necessary. There is also limited evidence pertaining to decompensated HF in particular. In this review, we synthesize current understandings around pathophysiology, prognostication and clinical management of heart failure (HF) patients, and also provide an outline of potential areas of future research and scientific advances.

Alcohol induced impairment/abnormalities in brain: Role of MicroRNAs.

Alcohol is a highly toxic substance and has teratogenic properties that can lead to a wide range of developmental disorders. Excessive use of alcohol can change the structural and functional aspects of developed brain and other organs. Which can further lead to significant health, social and economic implications in many countries of the world. Convincing evidence support the involvement of microRNAs (miRNAs) as important post-transcriptional regulators of gene expression in neurodevelopment and maintenance. They also show differential expression following an injury. MiRNAs are the special class of small non coding RNAs that can modify the gene by targeting the mRNA and fine tune the development of cells to organs. Numerous pieces of evidences have shown the relationship between miRNA, alcohol and brain damage. These studies also show how miRNA controls different cellular mechanisms involved in the development of alcohol use disorder. With the increasing number of research studies, the roles of miRNAs following alcohol-induced injury could help researchers to recognize alternative therapeutic methods to treat/cure alcohol-induced brain damage. The present review summarizes the available data and brings together the important miRNAs, that play a crucial role in alcohol-induced brain damage, which will help in better understanding complex mechanisms. Identifying these miRNAs will not only expand the current knowledge but can lead to the identification of better targets for the development of novel therapeutic interventions.

Joint preservation surgery in grade 2 and 3 giant cell tumors of bone around the knee.

OBJECTIVE: To evaluate the clinical and functional outcomes of joint preservation surgery in high-grade giant cell tumors (GCT) around the knee joint. METHODS: A retrospective review of 25 patients of high-grade GCT (Campanacci grade 2 and 3) involving proximal tibia or distal femur managed by extended curettage, bone grafting, and stabilization with knee spanning external fixator between 2016 and 2018 was done. The radiographic outcomes, functional outcomes (Musculoskeletal Tumor Society [MSTS] score for lower limb), and complications including donor site morbidity were evaluated. RESULTS: The mean age of the patient population was 24.04 years with an average follow-up period of 30.24 months. Fourteen patients had involvement of distal femur, and 11 involved proximal tibia. There were 16 cases of grade 2 lesions and 9 cases of grade 3 lesions. Twenty-four out of the 25 patients had radiological consolidation of graft, while one patient had graft subsidence. Twenty-two out of 25 patients had full extension and knee flexion more than 100 degrees. The mean MSTS score was 25.2. Three patients had an MSTS score under 20. All three patients had an extension lag with a restricted range of motion. CONCLUSION: Joint preservation surgery, when done in line with the basic principles of tumor surgery, gives good radiographic and functional outcomes even in grade 2 and 3 giant cell tumors of bone around the knee and should be attempted before replacement surgeries.

Neutrophil-lymphocyte ratio in acute ischemic stroke: Immunopathology, management, and prognosis.

There is an ongoing need for accurate prognostic biomarkers in the milieu of acute ischemic stroke (AIS) receiving reperfusion therapy. Neutrophil-lymphocyte ratio (NLR) has been implicated in emergency medicine and acute stroke setting as an important biomarker in the prognosis of patients. However, there are ongoing questions around its accuracy and translation into clinical practice given suboptimal sensitivity and specificity results, as well as varying thresholds and lack of clarity around which NLR time points are most clinically indicative. This article provides a comprehensive overview of the role of NLR in AIS patients receiving reperfusion therapy and perspectives on areas of future research. NLR may be an important biomarker in risk stratifying patients in AIS to identify and select those who are more likely to benefit from reperfusion therapy. Appropriate clinical decision-making tools and models are required to harness the predictive value of NLR, which could be useful in identifying and monitoring high-risk patients to guide early treatment and achieve improved outcomes. Our understanding of the role of NLR in the immunopathogenesis of AIS is also suboptimal, which hinders the ability to translate this into clinical practice.

Outcome Analysis of Fixed Angle Locking Plate in Patella Fractures: A Single Centre Experience from North India.

BACKGROUND: Tension band wiring supposedly is the most commonly used technique for displaced patella fractures, but is not effective in comminuted fractures and osteoporotic bones. It often leads to loosening of wires, dislocation of fracture, hardware problem and failure of osteosynthesis, resulting in knee stiffness and post-traumatic osteoarthritis. The aim of the study is to evaluate clinical outcome in patients with acute patella fractures (< 3 week) treated with unidirectional angle fixed low-profile titanium patella locking plate. MATERIALS AND METHODS: Twenty patients who presented with displaced patella fractures, aged between 18-70 years were included in the study. All fractures were reduced and fixed with unidirectional angle fixed stable low-profile titanium patella locking plate. Knee Range of motion and Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL) was used to evaluate the outcome. RESULTS: We were able to achieve union in 19 out of 20 patients. One patient with comminuted patella fracture had failure of fixation, which was revised. Mean flexion at final follow-up was 124° (110°-130°) and none of the patients had extensor lag. The final radiograph revealed complete union in all patients. CONCLUSION: This technique offers an option of fixation in comminuted patella fracture and in osteoporotic individuals. It provides mechanical stability for fracture fixation resulting in anatomical reduction, good functional outcome, lower incidence of symptomatic implant or failure of osteosynthesis.

Regulatory safety pharmacology and toxicity assessments of a standardized stem extract of Cassia occidentalis Linn. in rodents.

Cassia occidentalis Linn (CO) is an annual/perennial plant having traditional uses in the treatments of ringworm, gastrointestinal ailments and piles, bone fracture, and wound healing. Previously, we confirmed the medicinal use of the stem extract (ethanolic) of CO (henceforth CSE) in fracture healing at 250 mg/kg dose in rats and described an osteogenic mode of action of four phytochemicals present in CSE. Here we studied CSE's preclinical safety and toxicity. CSE prepared as per regulations of Current Good Manufacturing Practice for human pharmaceuticals/phytopharmaceuticals and all studies were performed in rodents in a GLP-accredited facility. In acute dose toxicity as per New Drug and Clinical Trial Rules, 2019 (prior name schedule Y), in rats and mice and ten-day dose range-finding study in rats, CSE showed no mortality and no gross abnormality at 2500 mg/kg dose. Safety Pharmacology showed no adverse effect on central nervous system, cardiovascular system, and respiratory system at 2500 mg/kg dose. CSE was not mutagenic in the Ames test and did not cause clastogenicity assessed by in vivo bone marrow genotoxicity assay. By a sub chronic (90 days) repeated dose (as per OECD, 408 guideline) study in rats, the no-observed-adverse-effect-level was found to be 2500 mg/kg assessed by clinico-biochemistry and all organs histopathology. We conclude that CSE is safe up to 10X the dose required for its osteogenic effect.

Short-term impacts of air pollutants in three megacities of India during COVID-19 lockdown.

Lockdown was imposed by the Indian government in the month of March 2020 as an early precaution to the COVID-19 pandemic which obstructed the socio-economic growth globally. The main aim of this study was to analyse the impact of lockdown (imposed in March and continued in April 2020) on the existing air quality in three megacities of India (Delhi, Mumbai and Kolkata) by assessing the trends of PM10 and NO2 concentrations. A comparison of the percentage reduction in concentrations of lockdown period with respect to same period in year 2019 and pre-lockdown period (February 14-March 24) was made. It was observed from the study that an overall decrease of pollutant concentrations was in the ranges of 30-60% and 52-80% of PM10 and NO2, respectively, in the three cities during lockdown in comparison with previous year and pre-lockdown period. The overall decrease in concentrations of pollutants at urban sites was greater than the background sites. Highest decline in concentrations of PM10 were observed in Kolkata city, followed by Mumbai and Delhi, while decline in NO2 was highest in Mumbai. Results also highlighted that capital city Delhi had the worst air quality amongst three cities, with particulate matter (PM10) being the dominant pollutant. Although COVID-19 has significantly affected the human life considering the mortality and morbidity, lockdowns imposed to control the pandemic had significantly improved the air quality in the selected study locations, although for the short amount of period.