The Consciousness State of Traditional Nidrâ Yoga/Modern Yoga Nidra: Phenomenological Characterization and Preliminary Insights from an EEG Study

Nidrâ yoga is an ancient yogic practice capable of inducing altered states of consciousness characterized by deep relaxation, strong concentration, acute self-awareness, and joy. In modern contemplative neuroscience language, it is known by the name yoga nidra, and few studies have investigated its phenomenological and psychophysiological effects. Six healthy volunteers (four females aged 31–74) performed 12 yoga nidra sessions guided by an expert during a 6-day retreat. Each session consisted of 10 minutes in a resting state (baseline) followed by 2 hours of yoga nidra. Psychometric data regarding dissociative experiences (Clinician Administered Dissociative States Scale) and the state of consciousness (Phenomenology of Consciousness Inventory) were collected after baseline and yoga nidra, while high-density EEG was recorded during the entire session. During nidra sessions, no sleep hallmarks (i.e., K-complexes and sleep spindles) were detected by the EEG in any subject. Psychometric data we re analyzed using a Wilcoxon signed-rank test corrected with the false discovery rate approach for multiple comparisons. Compared to baseline, yoga nidra practice was related to: (1) increased dissociative effects (p = 0.022); (2) perception of being in an altered state of consciousness (p = 0.026); (3) alterations in perceived body image (p = 0.022); (4) increased “meaningfulness” attributed to the experience (p = 0.026); (5) reduced rational thinking (p = 0.029); and (6) reduced volitional thought control (p = 0.026). First-person experience is discussed in relation to descriptive EEG power spectral density analysis, which was performed in one subject because of severe EEG artifacts in the other recordings; that subject showed, compared to baseline: (1) early increase of alpha and beta power, followed by a progressive widespread reduction; (2) widespread early increase of theta power, followed by a progressive reduction; and (3) widespread increase of gamma power in the latest stages. The present preliminary results enrich the knowledge of yoga nidra, elucidating its phenomenology and suggesting some psychophysiological correlates that future studies may address.

Igneous rock area and age in continental crust

Rock quantity and age are fundamental features of Earth’s crust that pertain to many problems in geoscience. Here we combine new estimates of igneous rock area in continental crust from the Macrostrat database (https://macrostrat.org/) with a compilation of detrital zircon ages in order to investigate rock cycling and crustal growth. We find that there is little or no decrease in igneous rock area with increasing rock age. Instead, igneous rock area in North America exhibits four distinct Precambrian peaks, remains low through the Neoproterozoic, and then increases only modestly toward the recent. Peaks in Precambrian detrital zircon age frequency distributions align broadly with peaks in igneous rock area, regardless of grain depositional age. However, detrital zircon ages do underrepresent a Neoarchean peak in igneous rock area; young grains and ca. 1.1 Ga grains are also overrepresented relative to igneous area. Together, these results suggest that detrital zircon age distributions contain signatures of continental denudation and sedimentary cycling that are decoupled from the cycling of igneous source rocks. Models of continental crustal evolution that incorporate significant early increase in volume and increased sedimentation in the Phanerozoic are well supported by these data.

Carnosic Acid Attenuates an Early Increase in ROS Levels during Adipocyte Differentiation by Suppressing Translation of Nox4 and Inducing Translation of Antioxidant Enzymes

The objective of this study was to investigate molecular mechanisms underlying the ability of carnosic acid to attenuate an early increase in reactive oxygen species (ROS) levels during MDI-induced adipocyte differentiation. The levels of superoxide anion and ROS were determined using dihydroethidium (DHE) and 2′-7′-dichlorofluorescin diacetate (DCFH-DA), respectively. Both superoxide anion and ROS levels peaked on the second day of differentiation. They were suppressed by carnosic acid. Carnosic acid attenuates the translation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4), p47phox, and p22phox, and the phosphorylation of nuclear factor-kappa B (NF-κB) and NF-κB inhibitor (IkBa). The translocation of NF-κB into the nucleus was also decreased by carnosic acid. In addition, carnosic acid increased the translation of heme oxygenase-1 (HO-1), γ–glutamylcysteine synthetase (γ-GCSc), and glutathione S-transferase (GST) and both the translation and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, these results indicate that carnosic acid could down-regulate ROS level in an early stage of MPI-induced adipocyte differentiation by attenuating ROS generation through suppression of NF-κB-mediated translation of Nox4 enzyme and increasing ROS neutralization through induction of Nrf2-mediated translation of phase II antioxidant enzymes such as HO-1, γ-GCS, and GST, leading to its anti-adipogenetic effect.

Angiopoietin-2 early increase to predict benefit from regorafenib in metastatic colorectal cancer (mCRC) patients: The prospective REGOLAND study.

e15566 Background: Regorafenib is a treatment option for refractory mCRC patients with no validated predictors of benefit. We previously showed that, among several circulating angiogenic factors, low baseline Ang-2 and Tie-2 plasma levels were associated with good prognosis and that the early increase of Ang-2 during the treatment could predict benefit from regorafenib ( Antoniotti et al, J Clin Oncol 36:675-675, 2018). To prospectively validate these retrospective findings, we conducted the REGOLAND study. Methods: Ang-2 and Tie-2 were assessed by ELISA on plasma samples collected at baseline (d1) and after 15 days (d15) of treatment in a cohort of mCRC patients receiving regorafenib, as per indication. To detect a HR for PFS of 0.50 in favour of the early increase (Δd15-d1) of Ang-2 levels, setting two-sided α = 0.05 and β = 0.10, 87 events were required according to Schoenfeld design. Comparisons among concentrations of each marker at d1 and d15 were performed by Wilcoxon test. Median values at baseline were used as cut-off to discriminate patients with low versus high plasma levels and their correlation with outcome was analysed. Results: One hundred patients were included. Median PFS and OS were 2.5 and 6.7 months, respectively. The early increase of Ang-2 at d15 was reported in 42 patients and was associated with longer PFS (median 2.7 vs 2.4 months; HR for PFS: 0.72 [95%CI:0.48-1.08], P = 0.095). As compared to d1, an overall decrease of Tie-2 levels at d15 was observed ( P = 0.007), but it was not associated with clinical outcome. Low levels of Ang-2 at baseline were associated with longer PFS (HR: 0.59 [95%CI:0.39-0.89], P = 0.005) and OS (HR:0.62 [95%CI:0.41-0.94], P = 0.017), while Tie-2 levels were not. In the multivariate model, the association of Ang-2 levels with PFS was confirmed (HR:0.48 [95%CI:0.31-0.76], P = 0.001), but not with OS (HR: 0.80 [95%CI:0.49-1.28], P = 0.351). Conclusions: Ang-2 is a prognostic marker and its early modulation predicts clinical benefit among mCRC patients treated with regorafenib. We hypothesize that Ang-2 levels early increase as a consequence of the successful inhibition of Tie-2 by regorafenib that leads to a compensatory increase of the ligand and correlates with anti-tumour activity.

Characterization of Two Ethephon-Induced IDA-Like Genes from Mango, and Elucidation of Their Involvement in Regulating Organ Abscission

In mango (Mangifera indica L.), fruitlet abscission limits productivity. The INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) peptide acts as a key component controlling abscission events in Arabidopsis. IDA-like peptides may assume similar roles in fruit trees. In this study, we isolated two mango IDA-like encoding-genes, MiIDA1 and MiIDA2. We used mango fruitlet-bearing explants and fruitlet-bearing trees, in which fruitlets abscission was induced using ethephon. We monitored the expression profiles of the two MiIDA-like genes in control and treated fruitlet abscission zones (AZs). In both systems, qRT-PCR showed that, within 24 h, both MiIDA-like genes were induced by ethephon, and that changes in their expression profiles were associated with upregulation of different ethylene signaling-related and cell-wall modifying genes. Furthermore, ectopic expression of both genes in Arabidopsis promoted floral-organ abscission, and was accompanied by an early increase in the cytosolic pH of floral AZ cells—a phenomenon known to be linked with abscission, and by activation of cell separation in vestigial AZs. Finally, overexpression of both genes in an Atida mutant restored its abscission ability. Our results suggest roles for MiIDA1 and MiIDA2 in affecting mango fruitlet abscission. Based on our results, we propose new possible modes of action for IDA-like proteins in regulating organ abscission.

Epidemiological characteristics of COVID-19 cases among Indians residing in Kuwait

Background: The coronavirus disease 2019 (COVID-19) pandemic has rapidly spread to most countries around the world. Disproportionate spread of COVID-19 among the Indian community in Kuwait prompted heightened surveillance in this community. Aims: To study the epidemiological characteristics of COVID-19 patients and their contacts among the Indian community in Kuwait. Methods: Data collection was done as a part of contact tracing efforts undertaken by the Kuwaiti Ministry of Health. Results: We analysed contact-tracing data for the initial 1348 laboratory-confirmed Indian patients and 6357 contacts (5681 close and 676 casual). The mean (standard deviation) age of the patients was 39.43 (10.5) years and 76.5% of the cases were asymptomatic or had only mild symptoms. Asymptomatic patients were significantly older [40.05 (10.42) years] than patients with severe symptoms [37.54 (10.54) years] (P = 0.024). About 70% of the patients were living in shared accommodation. Most of the close contacts were living in the same household, as compared with casual contacts, who were primarily workplace contacts (P < 0.001). Among the different occupations, healthcare workers had the highest proportion of cases (18.4%). Among the 216 pairs of cases with a clear relationship between the index and secondary cases, the mean serial interval was estimated to be 3.89 (3.69) days, with a median of 3 and interquartile range of 1–5 days. Conclusion: An early increase in the number of COVID-19 cases among the Indian community could be primarily attributed to crowded living conditions and the high proportion of healthcare workers in this community.

An Early Increase of Blood Leukocyte Subsets in Aneurysmal Subarachnoid Hemorrhage Is Predictive of Vasospasm

Objective: Vasospasm is a severe complication in patients with aneurysmal subarachnoid hemorrhage (aSAH) and cannot be reliably predicted. Its pathophysiology remains elusive with the current body of evidence suggesting inflammation as one of the main driving forces. We here aimed to analyze circulating immune cell subsets over time in patients with aSAH with or without vasospasm.Methods: We performed a prospective observational study recruiting patients with spontaneous aSAH. Peripheral blood withdrawn at pre-specified time-points after aSAH, day 0, days 3–4, 6–8, 10–11, 13–15, and 18–21. Flow cytometry analysis, cell blood counts, and laboratory and diagnostic parameters were performed. Patients were monitored by transcranial Doppler for vasospasm as well as by advanced imaging and divided into a group with (VS) and without vasospasm VS (NVS).Results: We included 42 patients for study analysis, 21 VS and 21 NVS. An early significant increase at day 0 in platelet, leukocyte, neutrophil, lymphocyte, NK lymphocyte, monocyte, and CD 14++ CD16− DR+ monocyte counts was found in patients with later ensuing vasospasm. The early differences in platelets, leukocytes, lymphocytes, and NK lymphocytes remained significant on multivariate analysis.Conclusions: An early increase of immune cellular subsets in aSAH may contribute to predict VS.

Changes in Bcl-2 members after ibrutinib or venetoclax uncover functional hierarchy in determining resistance to venetoclax in CLL

Chronic lymphocytic leukemia (CLL) cells cycle between lymph node (LN) and peripheral blood (PB) and display major shifts in Bcl-2 family members between those compartments. Specifically, Bcl-XL and Mcl-1, which are not targeted by the Bcl-2 inhibitor venetoclax, are increased in the LN. Because ibrutinib forces CLL cells out of the LN, we hypothesized that ibrutinib may thereby affect expression of Bcl-XL and Mcl-1 and sensitize CLL cells to venetoclax. We investigated expression of Bcl-2 family members in patients under ibrutinib or venetoclax treatment, combined with dissecting functional interactions of Bcl-2 family members, in an in vitro model of venetoclax resistance. In the PB, recent LN emigrants had higher Bcl-XL and Mcl-1 expression than did cells immigrating back to the LN. Under ibrutinib treatment, this distinction collapsed; significantly, the pretreatment profile reappeared in patients who relapsed on ibrutinib. However, in response to venetoclax, Bcl-2 members displayed an early increase, underlining the different modes of action of these 2 drugs. Profiling by BH3 mimetics was performed in CLL cells fully resistant to venetoclax due to CD40-mediated induction of Bcl-XL, Mcl-1, and Bfl-1. Several dual or triple combinations of BH3 mimetics were highly synergistic in restoring killing of CLL cells. Lastly, we demonstrated that proapoptotic Bim interacts with antiapoptotic Bcl-2 members in a sequential manner: Bcl-2 &gt; Bcl-XL &gt; Mcl-1 &gt; Bfl-1. Combined, the data indicate that Bcl-XL is more important in venetoclax resistance than is Mcl-1 and provide biological rationale for potential synergy between ibrutinib and venetoclax.