ß-keto amyrin isolated from Cryptostegia grandiflora R. br. inhibits inflammation caused by Daboia russellii viper venom: Direct binding of ß-keto amyrin to phospholipase A2.

The search for mechanism-based anti-inflammatory therapies is of fundamental importance to avoid undesired off-target effects. Phospholipase A2 (PLA2) activity is a potential molecular target for anti-inflammatory drugs because it fuels arachidonic acid needed to synthesize inflammation mediators, such as prostaglandins. Herein, we aim to investigate the molecular mechanism by which ß-keto amyrin isolated from a methanolic extract of Cryptostegia grandiflora R. Br. Leaves can inhibit inflammation caused by Daboia russellii viper (DR) venom that mainly contains PLA2. We found that ß-keto amyrin neutralizes DR venom-induced paw-edema in a mouse model. Molecular docking of PLA2 with ß-keto amyrin complex resulted in a higher binding energy score of -8.86 kcal/mol and an inhibition constant of 611.7 nM. Diclofenac had a binding energy of -7.04 kcal/mol and an IC50 value of 620 nM, which predicts a poorer binding interaction than ß-keto amyrin. The higher conformational stability of ß-keto amyrin interaction compared to diclofenac is confirmed by molecular dynamics simulation. ß-keto amyrin isolated from C. grandiflora inhibits the PLA2 activity contained in Daboia russellii viper venom. The anti-inflammatory property of ß-keto amyrin is due to its direct binding into the active site of PLA2, thus inhibiting its enzyme activity.

Solar roads - a new potential renewable energy for Great Britain.

Global warming has become a much more realised issue and an immediate threat, accelerating due to the anthropogenic carbon release associated with escalating energy demand. Consequently, pressures are building up to reduce anthropogenic carbon footprint by employing renewable energy resources, among which solar energy is the main. Solar roads are a new and innovative concept as they do not require land to be specifically allocated. This is because the road infrastructure already exists. Therefore, this emerging technique of embedding solar panels into pavements and roadways is becoming a more attractive proposition. However, a hurdle to its successful application is the lack of knowledge regarding its feasibility and viability. This study aims to evaluate the potential of solar roads to inform future feasibility and viability studies in varying contexts and implications. Within the scope of this study, the case of Great Britain is considered to evaluate the potential of how much energy can be generated via the solar roads technology that can be embedded in the country's road infrastructure. A mathematical exercise is performed in which calculations are executed to develop a basic numerical model of the potential. Therefore, the study is quantitative, and the factors considered include seasonal changes, average daily traffic covering roads, tree and building shades, road types and sizes, solar irradiance, solar panel types, and alike. It is estimated that solar roads may supply up to 96.42% of the UK's total electricity, which is a substantially promising potential.

Olfactomedin-4 + neutrophils exacerbate intestinal epithelial damage and worsen host survival after Clostridioides difficile infection.

Neutrophils are key first responders to Clostridioides difficile infection (CDI). Excessive tissue and blood neutrophils are associated with worse histopathology and adverse outcomes, however their functional role during CDI remains poorly defined. Utilizing intestinal epithelial cell (IEC)-neutrophil co-cultures and a pre-clinical animal model of CDI, we show that neutrophils exacerbate C. difficile -induced IEC injury. We utilized cutting-edge single-cell transcriptomics to illuminate neutrophil subtypes and biological pathways that could exacerbate CDI-associated IEC damage. As such, we have established the first transcriptomics atlas of bone marrow (BM), blood, and colonic neutrophils after CDI. We found that CDI altered the developmental trajectory of BM and blood neutrophils towards populations that exhibit gene signatures associated with pro-inflammatory responses and neutrophil-mediated tissue damage. Similarly, the transcriptomic signature of colonic neutrophils was consistent with hyper-inflammatory and highly differentiated cells that had amplified expression of cytokine-mediated signaling and degranulation priming genes. One of the top 10 variable features in colonic neutrophils was the gene for neutrophil glycoprotein, Olfactomedin 4 (OLFM4). CDI enhanced OLFM4 mRNA and protein expression in neutrophils, and OLFM4 + cells aggregated to areas of severe IEC damage. Compared to uninfected controls, both humans and mice with CDI had higher concentrations of circulating OLFM4; and in mice, OLFM4 deficiency resulted in faster recovery and better survival after infection. Collectively, these studies provide novel insights into neutrophil-mediated pathology after CDI and highlight the pathogenic role of OLFM4 + neutrophils in regulating CDI-induced IEC damage. One Sentence Summary: Utilizing single-cell transcriptomics, IEC-epithelial co-cultures, and pre-clinical models of CDI, we have identified a subset of neutrophils that are marked by OLFM4 expression as pathogenic determinants of IEC barrier damage after CDI.

True coincidence summing correction for a BEGe detector in close geometry measurements.

The true coincidence summing correction factor for a Broad Energy Germanium detector has been calculated at far and close geometry set-up using radioactive γ-ray sources. The correction factors were calculated using both experimental and analytical methods. Geant4 simulation was done to calculate the full-energy peak and total efficiencies of the detector. Standard, as well as fabricated mono-energetic γ-ray sources, were used for the γ-ray efficiency measurements. The simulated efficiencies of mono-energetic γ-ray sources were matched to the experimental γ-ray efficiencies by optimizing the detector parameters. The same parameters were used to obtain the full-energy peak and total efficiencies for γ-rays of current interest. Analytical and experimental correction factors were found to agree well with each other. The coincidence summing effect is found to be significant for source-to-detector distances less than 5 cm.

Nicotine limits avoidance conditioning with opioids without interfering with the ability to discriminate an opioid-interoceptive state.

Approximately 90 % of individuals undergoing treatment for opioid use disorder (OUD) report comorbid use of nicotine. As such, further investigation into underlying mechanisms contributing to the extreme comorbidity between nicotine and opioid use are warranted. Nicotine administration significantly escalates self-administration of opioids and this increase in motivational efficacy persists despite contingent punishment of opioid consumption. Additionally, both systemic and intra-insular administration of nicotine produces a rightward shift in the dose-response function in both morphine-induced conditioned place preference and taste avoidance paradigms, particularly at higher doses (5-20 mg/kg). Two possible interpretations arise from these outcomes. One is that nicotine may specifically affect learning about the malaise-inducing effects of morphine thus facilitating acceptance of higher doses of morphine. Another interpretation is that it more generally reduces sensitivity to the interoceptive effects of morphine such that higher doses are needed to produce comparable effects in nicotine-treated, relative to control, rats. To further address these possibilities, we asked whether nicotine administration interfered with the ability to discriminate the morphine interoceptive state, irrespective of its hedonic evaluation, at a dose that is impacted by nicotine in avoidance conditioning paradigms. First, we demonstrated that systemic nicotine pretreatment significantly attenuates taste avoidance induced by a low dose of morphine (3 mg/kg). Next, we used an occasion setting paradigm with this same dose of morphine to test whether systemic nicotine pretreatment interferes with the ability to discriminate between saline- and morphine-induced interoceptive states. Within this task, nicotine had no effect on the ability to effectively discriminate between the interoceptive effects of morphine and saline. Collectively, these data suggest that nicotine may be specifically altering the overall hedonic assessment of morphine perhaps by interfering with learning about its deleterious consequences.

Vaccination saves lives: a real-time study of patients with chronic diseases and severe COVID-19 infection.

OBJECTIVES: This study aims to describe the demographic and clinical profile and ascertain the determinants of outcome among hospitalized coronavirus disease 2019 (COVID-19) adult patients enrolled in the National Clinical Registry for COVID-19 (NCRC). METHODS: NCRC is an on-going data collection platform operational in 42 hospitals across India. Data of hospitalized COVID-19 patients enrolled in NCRC between 1st September 2020 to 26th October 2021 were examined. RESULTS: Analysis of 29 509 hospitalized, adult COVID-19 patients [mean (SD) age: 51.1 (16.2) year; male: 18 752 (63.6%)] showed that 15 678 (53.1%) had at least one comorbidity. Among 25 715 (87.1%) symptomatic patients, fever was the commonest symptom (72.3%) followed by shortness of breath (48.9%) and dry cough (45.5%). In-hospital mortality was 14.5% (n = 3957). Adjusted odds of dying were significantly higher in age group ≥60 years, males, with diabetes, chronic kidney diseases, chronic liver disease, malignancy and tuberculosis, presenting with dyspnoea and neurological symptoms. WHO ordinal scale 4 or above at admission carried the highest odds of dying [5.6 (95% CI: 4.6-7.0)]. Patients receiving one [OR: 0.5 (95% CI: 0.4-0.7)] or two doses of anti-SARS CoV-2 vaccine [OR: 0.4 (95% CI: 0.3-0.7)] were protected from in-hospital mortality. CONCLUSIONS: WHO ordinal scale at admission is the most important independent predictor for in-hospital death in COVID-19 patients. Anti-SARS-CoV2 vaccination provides significant protection against mortality.

Emphysematous cystitis: an incidental finding with varying outcomes.

Emphysematous cystitis (EC) is a rare severe urinary tract infection characterised by pockets of air in and around the urinary bladder wall caused by gas-forming organisms. Common predisposing factors are chronic infection, immunosuppression, diabetes and neurogenic bladder. The presentation may vary from mild illness to severe life-threatening cystitis. We report two cases of incidental detection of EC diagnosed on imaging for the evaluation of unrelated symptoms. Although asymptomatic, this lethal disease still warrants prompt recognition and treatment with broad-spectrum antibiotics and urinary bladder drainage to prevent severe morbidity and mortality.

Isoniazid preventive therapy among child contacts of TB patients, India.

BACKGROUND: Isoniazid preventive therapy (IPT) for child contacts of TB patients, a globally accepted intervention, needs to be evaluated in diverse geographical regions.OBJECTIVES: To assess the extent of IPT coverage and adherence, to ascertain its sociodemographic and programmatic correlates and to explore existing constraints from service providers and beneficiaries´ perspectives.METHODS: A mixed-method study was conducted in January-June 2021 in Paschim Bardhaman District, West Bengal, India. Quantitative assessment was done among 280 child contacts of TB cases registered between January and December 2020 in all TB units in the district. Primary caregivers were interviewed using a pre-designed questionnaire. Two focus group discussions with all senior treatment supervisors of the district and in-depth interviews with 12 purposively selected caregivers of the children were undertaken. Qualitative data were analysed thematically.RESULTS: Only 48.9% (137/280) of child contacts were screened; 58.9% (165/280) were initiated on IPT and 40% (66/165) adhered to a full course. Coverage of the full 6-month IPT among total study participants was 23.6% (66/280). Household visits by health personnel and initial screening significantly predicted increased coverage. Programmatic inadequacies, poor understanding, social stigma and COVID situation were major constraints.CONCLUSION: Coverage of IPT remains unacceptably low and requires health system strengthening for effectively implementing current recommendations of TB preventive treatment.

Impact of plasma glucose and duration of type 2 diabetes mellitus on SYNTAX Score II in patients suffering from non ST-elevation myocardial infarction.

Aim    The objective was to assess the correlation of fasting plasma glucose (FPG), HbA1c, and the duration of type 2 diabetes mellitus (T2DM) with SYNTAX score (SS) II in patients with non-ST elevation myocardial infarction (NSTEMI).Material and methods    FPG and HbA1C were measured in 398 patients presenting with NSTEMI at admission. SS II was calculated using an online calculator. Patients were stratified according to SS II (≤21.5, 21.5-30.6, and ≥30.6), defined as SS II low, mid, and high, respectively.Results    37.7 % of subjects were diabetic. Correlations of FPG (R=0.402, R2=0.162, p<0.001) and HbA1c (R=0.359, R2=0.129, p<0.001) with SS II were weak in the overall population. Duration of T2DM showed very strong correlation with SS II (R=0.827, R2=0.347). For the prediction of high SS II in the study population, FPG≥98.5 mg / dl demonstrated a sensitivity of 58 % and a specificity of 60 %, and HbA1c ≥6.05 demonstrated a sensitivity of 63 % and a specificity of 69 %. Duration of T2DM (adjusted odds ratio (OR): 1.182; 95 % confidence interval (CI): 1.185-2.773) and FPG (OR: 0.987; 95 % CI: 0.976-0.9959) were significantly associated with high SS II after controlling for other risk factors. Duration of T2DM (Beta=0.439) contributed strongly to variance of SS II, whereas HbA1c (Beta=0.063) contributed weakly.Conclusion    Duration of T2DM is a very important risk factor for severity of coronary artery disease.

On the varied emission fingerprints of particulate matter over typical locations of NCR (Delhi) - A perspective for mitigation plans.

Source apportionment study of PM2.5 using positive matrix factorization was performed to identify the emission characteristic from different sectors (sub-urban residential, industrial and rapidly urbanizing) of Delhi during winter. Chemical characterization of PM2.5 included metals (Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb and Zn), water soluble ionic compounds (WSICs) (Cl-, NO3-, SO42- and NH4+) and Carbon partitions (OC, EC). Particulates (PM2.5) were collected on filter twice daily for stable and unstable atmospheric conditions, at the locations with specific characteristics, viz. Ayanagar, Noida and Okhla. Ions solely occupied 50% of the total PM2.5 concentration. Irrespective of location, high correlation between OC and EC (0.871-0.891) at p ≤ 0.1 is observed. Relatively lower ratio of NO3/SO4 at Ayanagar (0.696) and Okhla (0.84) denotes predominance of emission from stationary sources rather than mobile sources like that observed at Noida (1.038). Using EPA PMF5.0, optimum factors for each location are fixed based on error estimation (EE). Crustal dust, vehicular emission, biomass burning and secondary aerosol are the major contributing sources in all the three locations. Incineration contributes about 19% at Ayanagar and 18% at Okhla. Metal industries in Okhla contribute about 19% to PM2.5. These specific local emissions with considerable potency are to be targeted for long-term policymaking. Considerable secondary aerosol contribution (15%-24%) indicates that gaseous emissions also need to be reduced to improve air quality.

Probing Flat Band Physics in Spin Ice Systems via Polarized Neutron Scattering.

In this Letter, we illustrate how polarized neutron scattering can be used to isolate the spin-spin correlations of modes forming flat bands in a frustrated magnetic system hosting a classical spin liquid phase. In particular, we explain why the nearest-neighbor spin ice model, whose interaction matrix has two flat bands, produces a dispersionless (i.e., "flat") response in the non-spin-flip (NSF) polarized neutron scattering channel and demonstrate that NSF scattering is a highly sensitive probe of correlations induced by weak perturbations that lift the flat band degeneracy. We use this to explain the experimentally measured dispersive (i.e., nonflat) NSF channel of the dipolar spin ice compound Ho_{2}Ti_{2}O_{7}.

Vitamin D repletion in primary hyperparathyroid patients undergoing parathyroidectomy leads to reduced symptomatic hypocalcaemia and reduced length of stay: a retrospective cohort study.

INTRODUCTION: Vitamin D deficiency co-exists with and can confuse the diagnosis of primary hyperparathyroidism (PHPT). Vitamin D replete (VDR) status may prevent significant postparathyroidectomy hypocalcaemia; however, reports from previous studies are conflicting. This study aimed to assess differences in early and/or late postoperative hypocalcaemia and length of stay (LOS) postparathyroidectomy between VDR and vitamin D non-replete (VDNR) PHPT patients. METHODS: This was a retrospective cohort study of a prospectively maintained single surgeon operative database. All records of patients who underwent parathyroidectomy over a four-year period (July 2014 to December 2018) were extracted. Data were collected on vitamin D and corrected calcium levels pre- and postoperatively as well as postoperative complications and LOS. RESULTS: On presentation, there were 91 (47.9%) VDR and 99 (52.1%) VDNR patients. Following vitamin D therapy there were 148 (77.9%) VDR and 42 (22.1%) VDNR. The multivariate analysis showed that vitamin D status was the only significant factor impacting on the hypocalcaemia symptoms (OR 4.9, 95% CI 1.8-13.7, p = 0.002) and the most significant factor for the calcium supplementation (OR 6.5, 95% CI 2.1-19.4, p = 0.001). Bilateral neck exploration was associated with increased likelihood of transient hypocalcaemia (p = 0.007) but no other post-op complication. Median LOS was significantly shorter for VDR (1 day) versus VDNR (1.5 days) patients (p = 0.001). CONCLUSION: There is a statistically significant increased likelihood of postoperative hypocalcaemia symptoms, requirement for calcium supplements and increased LOS in VDNR patients. This study suggests optimising preoperative vitamin D status improves patient experience and could reduce healthcare costs.

Microbial fuel cell performance for aromatic hydrocarbon bioremediation and common effluent treatment plant wastewater treatment with bioelectricity generation through series-parallel connection.

Microbial fuel cell (MFC) is an emerging technology which has been immensely investigated for wastewater treatment along with electricity generation. In the present study, the treatment efficiency of MFC was investigated for hydrocarbon containing wastewater by optimizing various parameters of MFC. Mediator-less MFC (1·2 l) was constructed, and its performance was compared with mediated MFC with Escherichia coli as a biocatalyst. MFC with electrode having biofilm proved to be better compared with MFC inoculated with suspended cells. Analysis of increasing surface area of electrode by increasing their numbers indicated increase in COD reduction from 55 to 75%. Catholyte volume was optimized to be 750 ml. Sodium benzoate (0·721 g l-1 ) and actual common effluent treatment plant (CETP) wastewater as anolyte produced 0·8 and 0·6 V voltage and 89 and 50% COD reduction, respectively, when a novel consortium of four bacterial strains were used. Twenty MFC systems with the developed consortium when electrically connected in series-parallel connection were able to generate 2·3 V and 0·5 mA current. This is the first report demonstrating the application of CETP wastewater in the MFC system, which shows potential of the system towards degradation of complex organic components present in industrial wastewater.

Surveillance of RNase P, PMMoV, and CrAssphage in wastewater as indicators of human fecal concentration across urban sewer neighborhoods, Kentucky.

Wastewater surveillance has been widely used as a supplemental method to track the community infection levels of severe acute respiratory syndrome coronavirus 2. A gap exists in standardized reporting for fecal indicator concentrations, which can be used to calibrate the primary outcome concentrations from wastewater monitoring for use in epidemiological models. To address this, measurements of fecal indicator concentration among wastewater samples collected from sewers and treatment centers in four counties of Kentucky (N = 650) were examined. Results from the untransformed wastewater data over 4 months of sampling indicated that the fecal indicator concentration of human ribonuclease P (RNase P) ranged from 5.1 × 101 to 1.15 × 106 copies/ml, pepper mild mottle virus (PMMoV) ranged from 7.23 × 103 to 3.53 × 107 copies/ml, and cross-assembly phage (CrAssphage) ranged from 9.69 × 103 to 1.85 × 108 copies/ml. The results showed both regional and temporal variability. If fecal indicators are used as normalization factors, knowing the daily sewer system flow of the sample location may matter more than rainfall. RNase P, while it may be suitable as an internal amplification and sample adequacy control, has less utility than PMMoV and CrAssphage as a fecal indicator in wastewater samples when working at different sizes of catchment area. The choice of fecal indicator will impact the results of surveillance studies using this indicator to represent fecal load. Our results contribute broadly to an applicable standard normalization factor and assist in interpreting wastewater data in epidemiological modeling and monitoring.

Bending of pinned dust-ion acoustic solitary waves in presence of charged space debris.

We consider a low temperature plasma environment in the low Earth orbital region in the presence of charged space debris particles. The dynamics of (2+1)-dimensional nonlinear dust-ion acoustic waves with weak transverse perturbation, generated in the system, is found to be governed by a forced Kadomtsev-Petviashvili equation, where the forcing term depends on charged space debris function. The bending phenomena of some exact dust-ion acoustic solitary wave solutions in the x-t and x-y planes are shown; they result from the consideration of different types of possible localized debris functions. A family of exact pinned accelerated solitary wave solutions has been obtained where the velocity changes over time but the amplitude remains constant. The shape of the debris function also changes during its propagation. Also, a special exact solitary wave solution has been derived for the dust-ion acoustic wave that gets curved in spatial dimensions with the curvature depending upon the nature of the forcing debris function. Such intricate solitary wave solutions may be useful in modeling real experimental data.

COVID-19 pandemic: mental health and beyond - the Indian perspective.

India is a de facto continent in the garb of a country. COVID-19 is an unprecedented global pandemic spanning continents. Being the second most populous country in the world, experts regard how India deals with the outbreak will have enormous impact on the world's ability to deal with it. The country has been in lockdown since March 25, 2020 until the current time of early May 2020, and despite several challenges, there has been early success. The major conflict now is the health benefits weighed up against the deleterious social and economic consequences of prolonged lockdown, that is, life versus livelihood. This unprecedented calamity could potentially cause or exacerbate various psychiatric disorders. It is recognized that lifestyle changes and limited screen time may help reduce mental health difficulties. Considering the physical barriers to consultation, development of telemedicine services is needed. This pandemic, like other previous pandemics, will pass, and until this happens, we must remain extremely vigilant.