Effective connectivity of LSD-induced ego dissolution

Classic psychedelic-induced ego dissolution involves a shift in the sense of self and blurring of boundary between the self and the world. A similar phenomenon is identified in psychopathology and is associated to the balance of anticorrelated activity between the default mode network (DMN) – which directs attention inwards – and the salience network (SN) – which recruits the dorsal attention network (DAN) to direct attention outward. To test whether change in anticorrelated networks underlie the peak effects of LSD, we applied dynamic causal modeling to infer effective connectivity of resting state functional MRI scans from a study of 25 healthy adults who were administered 100mg of LSD, or placebo. We found that change in inhibitory effective connectivity from the SN to DMN became excitatory, and inhibitory effective connectivity from DMN to DAN decreased under the peak effect of LSD. These changes in connectivity reflect diminution of the anticorrelation between resting state networks that may be a key neural mechanism of LSD-induced ego dissolution. Our findings suggest the hierarchically organised balance of resting state networks is a central feature in the construct of self.SignificanceThe findings can inform the parallel between the maintenance of subject-object boundary and changes to anticorrelated canonical resting state brain networks. Effective connectivity informs the hierarchical organisation of brain networks underlying modes of perception. Moreover, the anticorrelation of brain networks is an important measure of mental function. Understanding the neural mechanisms of anticorrelation change under psychedelics help identify its relationship to psychosis and its association to psychedelic assisted therapeutic outcomes.

(RE)Ba2Cu3O7–δ and the Roeser-Huber Formula

We apply the Roeser–Huber formula to the (RE)Ba2Cu3O7−δ (REBCO with RE= rare earths) high-Tc superconducting material class to calculate the superconducting transition temperature, Tc, using the electronic configuration and the crystallographic data. In a former publication (H. P. Roeser et al., Acta Astronautica 2008, 62, 733–736), the basic idea was described and Tc was successfully calculated for the YBa2Cu3O7−δ compound with two oxygen doping levels δ= 0.04 and 0.45, but several open questions remained. One of the problems remaining was the determination of Tc for the δ= 0.45 sample, which can be explained regarding the various oxygen arrangements being possible within the copper-oxide plane. Having established this proper relation and using the various crystallographic data on the REBCO system available in the literature, we show that the Roeser–Huber equation is capable to calculate the Tc of the various REBCO compounds and the effects of strain and pressure on Tc, when preparing thin film samples. Furthermore, the characteristic length, x, determined for the REBCO systems sheds light on the size of the δTc-pinning sites being responsible for additional flux pinning and the peak effect.

Resveratrol regulates cytokine secretion by cardiac microvascular endothelium under hypoxia/reoxygenation condition

Background Microvascular endothelial injury is recently considered playing an initial role in myocardial ischemia/reperfusion injury (MIRI). Cardiac microvascular endothelial cells (CMECs) regulate cardiomyocytes and haematocytes via secreting cytokine. MIRI jeopardize not only the barrier function but also the paracrine function of microvasculature. Resveratrol, a natural polyphenolic compound, was demonstrated to protect myocardium against MIRI and to preserve the function of endothelium. However, how the paracrine function of CMECs is regulated by MIRI and resveratrol remains to be elucidated. Purpose The study was to illuminate the alteration of cytokine profiles secreted by CMECs under hypoxia/reoxygenation (H/R) condition and its modulation by resveratrol. Methods CMECs were exposed to different concentrations of resveratrol for 30 minutes and then were subjected to H/R for 12 h/2 h. Apoptotic rates were measured to determine the optimal concentration. Protein antibody arrays were performed to find the alteration of cytokine secreted into conditioned medium by CMECs. A Gene Ontology (GO) analysis was applied to interpret the functional implication of changes in cytokine profiles. Results Resveratrol inhibited apoptosis of CMECs in a dose-dependent manner after H/R and reached its peak effect at the concentration of 100μM, which reduced apoptosis from 27.27±2.95% to 15.01±1.36% (Figure 1A and B). The results of a cluster analysis and all significantly altered factors are shown in figure 1C (fold-change >1.5; p<0.05). Twenty-nine types of cytokine were significantly changed by H/R (15 factors decreased and 14 increased, Figure 2A), and resveratrol at 100μM changed 98 types of cytokine compared with the H/R group (93 factors decreased and 5 increased, Figure 2B). Among these cytokine, eight factors were increased by H/R and they were decreased by resveratrol. Eleven were attenuated by H/R and further decreased by resveratrol. Insulin-like growth factor binding protein-1 was up-regulated by H/R and it was further increased by resveratrol (Figure 2C). The factors with significant alteration were involved in cellular growth, proliferation and differentiation, as well as chemotaxis and transport. Conclusions Resveratrol inhibited the apoptosis of CMECs and modulated the paracrine function of cardiac microvascular endothelium under ischemia/reperfusion condition. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation Figure 1 Figure 2

Modeling of Sea Surface Temperature through Fitting Linear Model with Interaction

Sea surface temperature (SST) is one of the attributes of the world climate system and global warming. The relationship between SST and other climate parameters can be represented in a linearity approach. Through this approach, SST variability shows monthly and yearly effects. Information on these two time effects is important for knowing the period of peak effect as well as other statistical measures in the linear fitting model. The models used include transformation and without covariate transformation, interaction and without covariate interaction, and with centering and with the addition of time covariates in the model. The linear fitting model chosen as the basis for construction is a model with a combination effect of covariate interaction and transformation giving an increase in the magnitude of multiple R2 (56.62%) and adjusted R2 (56.13%) respectively 0.31% and 0.43%. This indicates that the time covariate has a very strong significant effect on the model compared to the continuous covariate. In general, the model has a statistical significance of p-value < 2.2e-16, as well as for the time covariate. However, because the model has an autocorrelation and a large AIC value, this effect is removed by means of an autoregressive moving average. The obtained linear fitting model for SST data is the model with AIC 403.2987.

PHYTOCHEMICAL SCREENING AND EVALUATION OF ANTIDIARRHOEAL ACTIVITY OF BUNIUM BULBOCASTANUM SEEDS EXTRACT IN EXPERIMENTAL WISTAR RATS

Objective: The main objective of this study was to evaluate the antidiarrheal activity of Bunim bulbocastanum seeds extracts, to exploit the medicinal use of plant in the traditional system of medicine scientifically. Methods: The adult Wistar albino rats were divided in four groups, i.e. Group M1 (control group) receiving normal saline, group M2 (test group 1) receiving the 250 mg/kg Bunium bulbocastanum extract, group M2 (test group 2) receiving the 500 mg/kg Bunium bulbocastanum extract and group M4 (reference) receiving 3 mg/kg P. O Loperamide. Each group of mice with a bodyweight of 1 ml/100 g received castor oil. Mice were sacrificed and the distance traveled by the charcoal meal and the total length of the intestine was then measured. The peristaltic index and percentage of inhibition were calculated by using the formula. Results: It was found that in the castor oil-induced intestinal transit method extract produced a significant (p<0.0001) dose-dependent reduction in the distance traveled by charcoal meal comparable to the control peak effect was at the dose of 500 mg/kg (PI=12.06±3.38). Likewise, in the diarrheal dropping test, Bunium bulbocastanum extract causes a significant (p<0.05) dose-dependent reduction in the number of wet feces i.e. the mean wet of feces was decreased from 2.3±0.44 gm to 1.28±0.36 gm i.e. significantly different from that elicited by control (0.80±0.17 gm) (p=0.0081). However, there were no significant differences in inhibition at a dose of 250 mg/kg of extract. Conclusion: This study demonstrated that the crude methanol extract from B. bulbocastanum seeds possesses significant antidiarrheal property and the presence of various secondary metabolites. This justified the antidiarrheal use of plant in the traditional system of medicine.

Characterization of the genetic architecture of BMI in infancy and early childhood reveals age-specific effects and implicates pathways involved in Mendelian obesity

To elucidate the role of common genetic variation on infant and child weight development, we performed genome-wide association studies across 12 time points from birth to eight years in 28,681 children and their parents (27,088 mothers and 26,239 fathers) in the Norwegian Mother, Father and Child Cohort Study (MoBa). We identify 46 distinct loci associated with early childhood BMI at specific ages, matching different child growth phases, and representing four major trajectory patterns. Among these loci, 30 are independent of known birth weight and adult BMI loci, and 21 show peak effect between six months and three years, making these discoverable only at early age. Several of the 21 variants reside in/near genes previously implicated in severe forms of early-onset obesity, and monogenic obesity genes are enriched in the vicinity of the 46 loci. Four loci demonstrate evidence of several independent association signals as key drivers for BMI development near LEPR, GLP1R, PCSK1, and KLF14, all central to appetite and energy balance. At the KLF14 locus, we detect significant associations for maternally inherited alleles only, consistent with imprinting effects. Finally, we demonstrate how the BMI distribution stratified by different polygenic risk scores transitions from birth to adult profile throughout early childhood, and how age-specific polygenic risk scores improve the prediction of childhood obesity, outperforming scores based on adult BMI. In conclusion, our results offer a fine-grained characterization of the rapidly changing genetic association landscape sustaining early growth.

The effect of population mobility restrictive measures on the incidence of SARS-CoV-2 infection in the early phase of the pandemic

Background: This analysis aims to assess the association between population restrictive measures and the cumulative number of confirmed COVID-19 cases in the early phase of pandemic. Methods: We compared mobility data extracted from the Mobility Reports provided by Google with the cumulative number of confirmed cases of COVID-19 of 15 countries provided by John Hopkins University. We compared the number of confirmed COVID-19 cases before and after the peak effect (PE) of population mobility restrictions in each country, defined as the highest percent reduction in mobility measurements. Results: Time to PE of population mobility restrictions ranged between 16 and 45 days after the report of the index COVID-19 confirmed case in each country. The most frequent reductions in activities were retail & recreation, parks, and transit & stations, ranging from 30% to 90%. Despite this variability in PE among the countries, the predicted smooth effect after the PE of population mobility restrictions was observed in almost all countries. Conclusions: These data suggest that the reduction in mobility was associated with a decrease in the cumulative total number of COVI-19 cases in each country, underscoring that the use of widely available real-time surveillance data might be a valuable resource during this pandemic

ROTEM Analyses of Low Molecular heparin effects with Vitro Induced Thrombocytopenia

Background: Thrombocytopenia is correlated to hemorrhagic complications in patients with low molecular weight heparin (LMWH) thromboprophylaxis. Aims: The aims of our study were to investigate an experimentally induced in vitro thrombocytopenia and then adding 2 types of LMWHs in vitro. Our hypothesis was that a platelet depleted whole blood sample could reflect a stronger synergistic anticoagulative effect of in vitro added LMWH than in the non-manipulated blood. Method: Two venous citrated blood samples were consecutively drawn from 8 patient’s gynaecologic cancer and normal routine coagulation laboratory analyses immediately preopewratively. One of the two samples had its buffy coat pipetted away into a separate tube. Half of the buffy coat was returned to the same sample (treated sample). 3x500 μl of blood from the non-treated sample was added to 3 separate microtubes and corresponding for the treated sample. Thromboprophylactic doses corresponding to an in vivo peak effect 0.5 anti-Xa international units/ml of tinzaparin and enoxaparin were added both to untreated and treated samples – 2 microtubes were unheparinized (treated/untreatedsample). All samples were analysed with rotational thromboelastometry (ROTEM). Results: Wilcoxon matched-pairs signed rank tests of the in-group differences between non-non-treated and treated samples showed no significant differences (p≤0.05) for any of the parameters analysed with the ROTEM-INTEM reagent regardless of heparinization or not. Calculation of non-parametric spearman correlation for clotting time (CT) vs. platelet count (PLC) were not significant for any group. Tinzaparin was clearly observed to prolong CT in the buffy-coat lowered blood from two patients. Conclusions: Our results corroborate previous research that ROTEM cannot detect anticoagulative effects of low dose LMWH in patients with normal PLC. In two patients there was a clear prolongation of clot initiation after tinzaparin that warrants further studies on a more developed in vitro induced thrombocytopenia model.