ABSTRACT
BackgroundThe second COVID-19 wave in India, triggered by the Delta variant,has been associated with an unprecedented increase in cases of COVID-19 associated Mucormycosis(CAM), mainly Rhino-orbito-cerebral mucormycosis(ROCM).The primary reason appears to be an unusual alignment of multiple risk factors in patients like prevalence of hypoxia, uncontrolled diabetes mellitus, indiscriminate use of steroids, high iron levels and immune dysfunction. MethodsThis retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC), Pune, Western India between 1st April 2020 and 1st August 2021 to identify patients admitted with CAM. The primary endpoint was incidence of all cause mortality due to CAM. Secondary outcomes studied were need for mechanical ventilation and intensive care unit(ICU) admission. Baseline and time dependent risk factors significantly associated with death due to CAM were identified by Relative risk estimation. Results59 patients were diagnosed with Mucormycosis at NHRC (58 ROCM, 1 Renal (disseminated) mucormycosis). Median age of the cohort was 52(IQR: 41,61) years and it included 20.3% females. Median duration from first positive COVID-19 RT PCR test to diagnosis of Mucormycosis was 17(IQR: 12,22) days. 90% patients were diabetic with 30% being newly diagnosed at the time of COVID-19 admission and 89% having uncontrolled sugar level (HbA1c > 7%). All patients were prescribed steroids during treatment for COVID-19. 56% patients were prescribed steroids for non-hypoxemic, mild COVID (irrational steroid therapy) while in 9%, steroids were indicated but were prescribed in inappropriately high dose. Majority of the patients were treated with a combination of surgical debridement(94%), intravenous Amphotericin B(91%) and concomitant oral Posoconazole therapy(95.4%). 74.6% patients were discharged after clinical and radiologic recovery while 25.4% (15 patients) died. On Relative risk analysis, CT severity score during COVID-19 admission [≥]18 (p=0.017), presence of orbital symptoms(p=0.002), presence of diabetic ketoacidosis(p=0.011) and cerebral involvement by Mucor(p=0.0004) were associated with increased risk of death. Duration of Amphotericin B therapy of [≥] 21 days was associated with statistically significant reduction in mortality(p=0.002). ConclusionsCAM is an uncommon, rapidly progressive, angioinvasive, opportunistic fungal infection which is fatal if left untreated. Combination of surgical debridement and antifungal therapy leads to clinical and radiologic improvement in majority of cases.
ABSTRACT
Despite Nitrous oxide (N2O) being the most widely used anesthetics in dental and other medical applications, it is associated with global warming and stratospheric ozone destruction. With globalization, a larger amount of N2O emissions arearticulated especially from human activities (30%, 6.7 Tg N per year), which are primarily dominated by agriculture that is even above the emissions of all oceans (26%). The synthesis of N2O reflects the general chemistry and readily from a substrate Nitric oxide (NO) in the environment. The modeling of infectious disease dynamics covering common pathogen-transmission factors, for example intrinsic (or microbes nutrient supply) at a population level, is indeed imperative to curb the menace of any disease. Nonetheless, in areas where novel coronavirus disease (COVID-19) was at its worst, for example, Wuhan China, Mumbai India, Milan Italy, Washington USA etc., the reduction in N2O emissions was well noticed. Nonetheless, viruses exhibit greater mobility than humans and hijack nutrients including nitrogen to complete their epidemiological cycle all due to limited sequence space of viral genomes, the high probability of genetic drift, extremely large population sizes, the high mutation and recombination rates. In consequence of drastic fall in N2O emissions, lower human transport can not be an all alone contributor, but contrarily it may also be associated with coronavirus intrinsic factors. This prompted us to analyze freely accessible and large global data from two authenticated sources, the World Health Organization and World Bank. We hereby argue that intrinsic factor N2O emissions fueling the COVID-19 progression significantly. Entire predictions were found consistent with the recently observed shreds of evidence. These insights enhanced scientific ability to interrogate viral epidemiology and recommended a 7-points framework covering all-natural lifestyle and dietary supplements for COVID-19 prevention before the arrival of a front-line therapeutic(s) or preventable vaccine.
ABSTRACT
Advances in our understanding of complex COVID-19 pandemic would allow us to effectively eliminate and eradicate SARS-COV2 virus. Although tremendous amount of research devoted to the robustness across its biology, diagnostics, vaccines and treatment has exploded in the past two years. However, still science do not have robust answers for causes, for example (i) What are the reasons of non-uniform global distribution of COVID-19? (ii) Why the United States, India, and Brazil, are the first-three most affected nations?, (iii) How did Bhutan, a nation sharing a boundary with China manage nearly 0.34% infections and 3 deaths from COVID-19? Nonetheless, the biomass bistribution of biosphere report suggest more than 1550-fold larger microbial biomass involving bacteria, fungi, archaea, protists and viruses is exist in comparision to all global human population in the biosphere. The rich microbiota act a first line of defence to invade pathogens and affect us both through the environment and microbiome. Unfortunately, a role of pathogen-transmission factors viz. implicit factors (competitive microflora) is still under represented. This study is an attempt from a gold standard correlation methodology using a large pesticide use global data. The non-specific pesticides kill both pests as well as protective microbiota, resulting a loss in rich biodiversity and allow easy pathogen entry to human. Entire predictions were found consistent with the recently observed evidences. These insights enhanced scientific ability to interrogate viral epidemiology and recommended to limit pesticide use for future pandemic prevention.
ABSTRACT
Coronavirus disease 19 (Covid-19) is causing a dramatic impact on human life worldwide. As of June 11 2021, later one has attributed more than 174 million confirmed cases and over 3.5 million deaths globally. Nonetheless, a World Bank Group flagship report features Covid-19 induced global crisis as the strongest post-recession since World WarII. Currently, all approved therapeutics or vaccines are strictly allowed for emergency use. Hence, in the absence of pharmaceutical interventions, it is vital to analyze data set covering the growth rates of positive human cases, number of recoveries, other factors, and future strategies to manage the growth of fatal Covid-19 effectively. The Uttarakhand state of India is snuggled in the lap of the Himalayas and occupies more people than Israel, Switzerland, Hong Kong, etc. This study analyzed state Covid-19 data, fetched from an authenticated government repository using Python 3.9 from April 1, 2020, to February 28, 2021. In the first wave, plain areas of Uttarakhand covering the districts Dehradun, Haridwar, Nainital, and U. S. Nagar were severely affected and reported peak positive cases during the 21st - 26th week. Other hands, the hilly terrains of Uttarakhand districts, including Chamoli, Pauri Garhwal, and Rudraprayag, reported a high number of positive cases between the 30th and 31st week, and other hilly districts reported an increase in Covid-19 cases during the 34th to 38th week. The highest recovery rate was attributed to the hilly district Rudraprayag. The analysis also revealed that a very high doubling rate was seen during the last week of May to the first week of Jun 2020. At last, based on this blueprint, we have suggested 6-points solutions for preventing the next pandemic.
ABSTRACT
BackgroundCytokine release syndrome (CRS) or cytokine storm is thought to be the cause of inflammatory lung damage, worsening pneumonia and death in patients with COVID-19. Steroids (Methylprednisolone or Dexamethasone) and Tocilizumab (TCZ), an interleukin-6 receptor antagonist, are approved for the treatment of CRS in India. The aim of this study was to evaluate the efficacy and safety of combination therapy of TCZ and steroids in COVID-19 associated CRS. MethodsThis retrospective cohort study was conducted at a tertiary level private hospital in Pune, India between 2nd April and 2nd November 2020. All patients administered TCZ and steroids for treatment of CRS were included. The primary endpoint was incidence of all-cause mortality. Secondary outcomes studied were need for mechanical ventilation and incidence of infectious complications. Baseline and time-dependent risk factors significantly associated with death were identified by Relative risk estimation. ResultsOut of 2831 admitted patients, 515 (24.3% females) were administered TCZ and steroids. Median age of the cohort was 57 (IQR: 46.5, 66) years. Almost 72 % patients had preexisting co-morbidities. Median time to TCZ administration since onset of symptoms was 9 days (IQR: 7, 11). 63% patients needed intensive care unit (ICU) admission. Mechanical ventilation was required in 242 (47%) patients. Of these, 44.2% (107/242) recovered and were weaned off the ventilator. There were 135 deaths (26.2%), while 380 patients (73.8%) had clinical improvement. Infectious complications like hospital acquired pneumonia, bloodstream bacterial and fungal infections were observed in 2.13 %, 2.13 % and 0.06 % patients respectively. Age [≥] 60 years (p=0.014), presence of co-morbidities like hypertension (p = 0.011), IL-6 [≥] 100 pg/ml (p = 0.002), D-dimer [≥] 1000 ng/ml (p < 0.0001), CT severity index [≥] 18 (p < 0.0001) and systemic complications like lung fibrosis (p = 0.019), cardiac arrhythmia (p < 0.0001), hypotension (p < 0.0001) and encephalopathy (p < 0.0001) were associated with increased risk of death. ConclusionsCombination therapy of TCZ and Steroids is likely to be safe and effective in the management of COVID-19 associated cytokine release syndrome. Efficacy of this anti-inflammatory combination therapy needs to be validated in randomized controlled clinical trials.
ABSTRACT
BACKGROUND: Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles. RESULTS: Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content. CONCLUSION: Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.
