AMIODARONE INDUCED OXIDATIVE STRESS IN STRESS - VULNERABLE ORGANS OF ADULT MALE RATS

Objective: Amiodarone used as an antiarrhythmic agent bears a structural resemblance to thyroid hormones containing about one-third iodine byweight. The pro-oxidant potentialities of amiodarone induced changes were studied.Materials and Methods: Male adult Wister rats were divided into two groups of eight animals each, and amiodarone was supplemented orallyfor 30 days against control. The urinary iodine content of both the groups was measured. Animals were sacrificed after completion of treatment;investigated parameters were adrenal morphology and histology, adrenal Δ5 3β hydroxyl steroid dehydrogenase (HSD) and serum cortisol level.Superoxide dismutase (SOD), catalase and lipid peroxidation (LPO) level were assayed in the liver, kidney and testis along with their histology. Serumglutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvate transaminase (SGPT) were measured. Obtained results were interpreted againstthe control group of rats.Results: Urinary iodine level was high after the amiodarone exposure. Hypertrophied cortex with enhanced Δ5 3β HSD activity in adrenal causedelevated serum cortisol level. Amiodarone exposure had increased LPO level with a concomitant rise in catalase and SOD activities in liver, kidney andtestis in comparison to control (p<0.001). Simultaneously kidney showed shrinkage of the glomerulus, in liver the area surrounding the central canalfound disrupted and in the testis seminiferous tubules, and germ cells were disorganized in comparison to control. SGOT and SGPT level were foundelevated in the treated group.Conclusion: Amiodarone exposure develops stress for the metabolism and deiodinization of amiodarone releasing excessive iodine in circulationthat in turn generates reactive oxygen species and free radicals resulting cellular damage of stress vulnerable organs.Keywords: Amiodarone, Excess iodine, Hypertrophied adrenal, Cellular damage, Stress-vulnerable organs, Reactive oxygen species

Local shell-to-shell energy transfer via nonlocal Interactions in fluid turbulence

In this paper we analytically compute the strength of nonlinear interactions in a triad, and the energy exchanges between wavenumber shells in incompressible fluid turbulence. The computation has been done using first-order perturbative field theory. In three dimension, magnitude of triad interactions is large for nonlocal triads, and small for local triads. However, the shell-to-shell energy transfer rate is found to be local and forward. This result is due to the fact that the nonlocal triads occupy much less Fourier space volume than the local ones. The analytical results on three-dimensional shell-to-shell energy transfer match with their numerical counterparts. In two-dimensional turbulence, the energy transfer rates to the near-by shells are forward, but to the distant shells are backward; the cumulative effect is an inverse cascade of energy.Comment: 10 pages, Revtex

Application of frequency ratio, statistical index, and weights-of-evidence models and their comparison in landslide susceptibility mapping in Central Nepal Himalaya

The Mugling–Narayanghat road section falls within the Lesser Himalaya and Siwalik zones of Central Nepal Himalaya and is highly deformed by the presence of numerous faults and folds. Over the years, this road section and its surrounding area have experienced repeated landslide activities. For that reason, landslide susceptibility zonation is essential for roadside slope disaster management and for planning further development activities. The main goal of this study was to investigate the application of the frequency ratio (FR), statistical index (SI), and weights-of-evidence (WoE) approaches for landslide susceptibility mapping of this road section and its surrounding area. For this purpose, the input layers of the landslide conditioning factors were prepared in the first stage. A landslide inventory map was prepared using earlier reports, aerial photographs interpretation, and multiple field surveys. A total of 438 landslide locations were detected. Out these, 295 (67 %) landslides were randomly selected as training data for the modeling using FR, SI, and WoE models and the remaining 143 (33 %) were used for the validation purposes. The landslide conditioning factors considered for the study area are slope gradient, slope aspect, plan curvature, altitude, stream power index, topographic wetness index, lithology, land use, distance from faults, distance from rivers, and distance from highway. The results were validated using area under the curve (AUC) analysis. From the analysis, it is seen that the FR model with a success rate of 76.8 % and predictive accuracy of 75.4 % performs better than WoE (success rate, 75.6 %; predictive accuracy, 74.9 %) and SI (success rate, 75.5 %; predictive accuracy, 74.6 %) models. Overall, all the models showed almost similar results. The resultant susceptibility maps can be useful for general land use planning

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Effects of magnesium on cytomorphology and enzyme activities in thyroid of rats

787-792Till date knowledge regarding the effects of high dietary magnesium on thyroid gland is incomprehensive though certain epidemiological studies reported development of thyroid gland dysfunctions in people with chronic exposure to hard water (especially with high magnesium) despite sufficient iodine consumption. The present study is to explore the effects of chronic high dietary magnesium exposure on thyroid morphology and functional status. Male adult albino Wistar strain rats were treated with graded doses of magnesium sulphate (MgSO4; 0.5, 1.0 and 1.5 g %) for 60 days and changes in different thyroid parameters were investigated. Significantly stimulated thyroid peroxidase and Na+–K+-ATPase and altered idothyronine 5/- deiodinase type I activities, enhanced serum thyroxine (T4) (both total and free), total triiodothyronine (T3) and thyroid stimulating hormone with decreased free T3 levels and T3/T4 ratio (T3:T4) along with enlargement of thyroid with associated histopathological changes were observed in the treated groups. The results clearly confirm that chronic high dietary magnesium exposure causes potential thyroid disruption as reported in earlier epidemiological studies. </span