Yoga Intervention as a Potential Countermeasure for Polar T3 Syndrome

Polar T3 syndrome is a common ailment for polar sojourners. It is characterised by abnormal fluctuations of thyroid hormones during extended polar winter. A randomised controlled study was conducted on 14 winter expedition members of Indian Scientific Expedition (2016) to Antarctica by introducing customised yoga module. Blood samples were collected during January to October, 2016 at different intervals for the estimation of total thyroxine (TT4), total triiodothyronine (TT3), thyroid stimulating hormone and noradrenaline (NA) by ELISA. In October yoga group showed significant (p = 0.04) higher TT3 values (2.1 ng/ml ± 0.9; mean ± SD) as compared to the control (0.7 ng/ml ± 0.6). In October a significant difference (p=0.0085) was observed between yoga and control group for NA values (47.0 pg/ml ± 22.0 and 107 pg/ml ± 46.0). Thyroid response of control group at the end of the study revealed presence of polar T3 syndrome in control group. Results indicate that regular yoga practice helped mitigating polar T3 syndrom

Cytokines and Inflammatory Mediators [30-39]: 30. The LPS Stimulated Production of Interleukin-10 is not Associated with -819C/T and -592C/A Promoter Polymorphisms in Healthy Indian Subjects

Background: Interleukin-10 is a pivotal immunoregulatory cytokine with pleiotropic effects on the immune system. IL-10 promoter polymorphisms have been associated with disease susceptibility and the ability to secrete IL-10 in vitro. We suspected that the association of the widely studied -819C/T and -592C/A polymorphisms with the IL-10 production might vary between ethnic groups. Therefore, we examined the association of -819 C/T and -592 C/A promoter polymorphisms with in vitro LPS stimulated secretion of IL-10 in normal healthy Indian volunteers. Methods: Peripheral blood was collected from 103 healthy volunteers and diluted whole blood cultures were set up with 100 ng/ml of LPS as stimulant: supernatant was collected at 24 h and IL-10 levels were assayed by ELISA. Genotyping was done for -819C/T polymorphism in 101 individuals and -592C/A polymorphism in 68 individuals by polymerase chain reaction followed by RFLP. The differences in IL-10 production between the genotypes were analysed by ANOVA. Results: There were 30, 47 and 24 individuals with the CC, CT and TT genotypes with a minor allele (T) frequency of 47% for the -819C/T polymorphism. The CC and TT genotypes at position -819 were strongly associated with CC and AA genotypes at -592 position suggestive of strong linkage disequilibrium. There was no association between the -819 genotype and the in vitro LPS stimulated IL-10 levels. Conclusions: The -819C/T and the -592 C/A polymorphisms of the IL-10 promoter region are not significantly associated with LPS stimulated IL-10 production healthy Indian subjects. Disclosure statement: All authors have declared no conflicts of interes

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Experimental and theoretical study of intramolecular O center dot center dot center dot O interaction in structurally rigid beta-keto carboxylic esters

Here we report the crystal structures of quinolone carboxylate and bisethoxycarbonylvinylaniline derivates containing an O center dot center dot center dot O distance shorter than the sum of their van der Waals radii, which can be ascribed to their steric demand per se, which provide unequivocal evidence of intramolecular 1,5-closed shell type interaction. Theoretical studies including Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbital (NBO) analysis are employed to characterize the nature of the closed shell O center dot center dot center dot O interaction. We found that the lone pair electrons on the interacting oxygens undergo stabilization due to negative hyperconjugation and maintains the otherwise repulsive O center dot center dot center dot O close contact

Experimental and Computational Studies of the Flow Over a Sting Mounted Planetary Probe Configuration

This paper summarizes the results of a series of experimental studies in the LENS shock tunnel and computations with DSMC and Navier Stokes codes which have been made to examine the aerothermal and flowfield characteristics of the flow over a sting-supported planetary probe configuration in hypervelocity air and nitrogen flows. The experimental program was conducted in the LENS hypervelocity shock tunnel at total enthalpies of 5and 10 MJkg for a range of reservoir pressure conditions from 70 to 500 bars. Heat transfer and pressure measurements were made on the front and rear face of the probe and along the supporting sting. High-speed and single shot schlieren photography were also employed to examine the flow over the model and the time to establish the flow in the base recirculation region. Predictions of the flowfield characteristics and the distributions of heat transfer and pressure were made with DSMC codes for rarefied flow conditions and with the Navier-Stokes solvers for the higher pressure conditions where the flows were assumed to be laminar. Analysis of the time history records from the heat transfer and pressure instrumentation on the face of the probe and in the base region indicated that the base flow was fully established in under 4 milliseconds from flow initiation or between 35 and 50 flow lengths based on base height. The measurements made in three different tunnel entries with two models of identical geometries but with different instrumentation packages, one prepared by NASA Langley and the second prepared by CUBRC, demonstrated good agreement between heat transfer measurements made with two different types of thin film and coaxial gage instrumentation. The measurements of heat transfer and pressure to the front face of the probe were in good agreement with theoretical predictions from both the DSMC and Navier Stokes codes. For the measurements made in low density flows, computations with the DSMC code were found to compare well with the pressure and heat transfer measurements on the sting, although the computed heat transfer rates in the recirculation region did not exhibit the same characteristics as the measurements. For the 10MJkg and 500 bar reservoir match point condition, the measurements and heat transfer along the sting from the first group of studies were in agreement with the Navier Stokes solutions for laminar conditions. A similar set of measurements made in later tests where the model was moved to a slightly different position in the test section indicated that the boundary layer in the reattachment compression region was close to transition or transitional where small changes in the test environment can result in larger than laminar heating rates. The maximum heating coefficients on the sting observed in the present studies was a small fraction of similar measurements obtained at nominally the same conditions in the HEG shock tunnel, where it is possible for transition to occur in the base flow, and in the low enthalpy studies conducted in the NASA Langley high Reynolds number Mach 10 tunnel where the base flow was shown to be turbulent. While the hybrid Navier- StokedDMSC calculations by Gochberg et al. (Reference 1) suggested that employing the Navier- Stokes calculations for the entire flowfield could be seriously in error in the base region for the 10 MJkg, 500 bar test case, similar calculations performed by Cornell, presented here, do not