Effect of cimetidine, ranitidine, famotidine and omeprazole on hepatocyte proliferation in vitro

Recently reports have indicated that both cimetidine and ranitidine delay cell proliferation in rats following 70% partial hepatectomy and result in an increased mortality following this procedure. The present study was designed to determine whether three H2 blocking agents (cimetidine, ranitidine, famotidine) and a new, powerful antisecretory drug (omeprazole) specifically influence hepatocyte proliferation in primary culture. Hepatocytes were isolated from livers of normal male rats by the standard collagenase perfusion technique. Hepatic DNA synthesis and percent of labelled nuclei were determined after 48 h incubation. Hepatocytes in culture were incubated with the H2 blocking agents and omeprazole or with different concentrations of serum obtained from shamoperated or 70% hepatectomized rats treated or not with the same agents. Rats were injected intraperitoneally at 8:00 a.m. on two consecutive days. In hepatectomized rats, the first dose was injected at 8:00 a.m. immediately after surgery, the second, 24 h later. The serum of sham-operated or 70% hepatectomized rats that did not receive drugs served as control. No changes in DNA synthesis, percentage of labelled nuclei and transaminase were detected when the agents were added to the hepatocytes in culture at concentrations within the effective pharmacological dosage and 30 times higher. Similarly, no changes in these parameters were obtained when different concentrations of serum obtained from sham-operated rats treated with H2 blocking agents or omeprazole were added to the basal culture medium. However, a significant inhibition of DNA synthesis and of percentage of labelled nuclei was observed when hepatocytes were incubated in the presence of serum from 70% hepatectomized rats that had been treated with cimetidine or with ranitidine. The serum of 70% hepatectomized rats treated with famotidine and omeprazole had no effect on hepatocyte proliferation in vitro. No effect on transaminase was found in these conditions. © 1989

Verifying nomenclature of DNA variants in submitted manuscripts: guidance for journals

Documenting variation in our genomes is important for research and clinical care. Accuracy in the description of DNA variants is therefore essential. To address this issue, the Human Variome Project convened a committee to evaluate the feasibility of requiring authors to verify that all variants submitted for publication complied with a widely accepted standard for description. After a pilot study of two journals, the committee agreed that requiring authors to verify that variants complied with Human Genome Variation Society nomenclature is a reasonable step toward standardizing the worldwide inventory of human variation.Molecular Technology and Informatics for Personalised Medicine and Healt

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)

How decision reversibility affects motivation

The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making, strengthening prevention-related motivation relatively more than promotion-related motivation. If so, then decision reversibility should have effects associated with the relative differences between prevention and promotion motivation. In 5 studies, we manipulated the reversibility of a decision and used different indicators of regulatory focus motivation to test these predictions. Specifically, Study 1 tested for differences in participants' preference for approach versus avoidance strategies toward a desired end state. In Study 2, we used speed and accuracy performance as indicators of participants' regulatory motivation, and in Study 3, we measured global versus local reaction time performance. In Study 4, we approached the research question in a different way, making use of the value-from-fit hypothesis (Higgins, 2000, 2002). We tested whether a fit between chronic regulatory focus and focus induced by the reversibility of the decision increased participants' subjective positive feelings about the decision outcome. Finally, in Study 5, we tested whether regulatory motivation, induced by decision reversibility, also influenced participants' preference in specific product features. The results generally support our hypothesis showing that, compared to irreversible decisions, reversible decisions strengthen a prevention focus more than a promotion focus. Implications for research on decision making are discussed

The Perfect Mix: Regulatory Complementarity and the Speed-Accuracy Balance in Group Performance

In this research, we varied the composition of 4-member groups. One third of the groups consisted exclusively of "locomotors," individuals predominantly oriented toward action. Another third of the groups consisted exclusively of "assessors," individuals predominantly oriented toward evaluation. The final third of the groups consisted of a mix of locomotors and assessors. We found that the groups containing only locomotors were faster than the groups containing only assessors, and the groups containing only assessors were more accurate than the groups containing only locomotors. The groups containing a mix of assessors and locomotors were as fast as the groups containing only locomotors and as accurate as the groups containing only assessors. These results echo findings at the individual level of analysis, and suggest that the testing and action components of operating systems independently contribute to performance both intra- and interpersonally

Stereoscopic observations of Jovian decametric radio arc s associated with ultraviolet auroras

Auroras in Jupiter’s polar regions show complex activity over a broad range of electromagnetic wavelengths. One of the auroral radio components, decametric radiation (DAM), dominates the frequency range from a few to 40 MHz and is produced at a frequency very close to the local electron cyclotron frequency. Since Juno first began detecting sporadic DAM arcs on May 5, 2016, during the approach to Jupiter, the DAM radio arcs have been monitored in a frequency range of 3.5 to 40.5 MHz by several observatories. These include Juno at Jupiter, Cassini at Saturn, STEREO A at 1 AU, WIND at Earth, and Earth-based radio observatories (Long Wavelength Array Station One (LWA1) in New Mexico, USA, and Nançay Decameter Array (NDA) in France). We have carried out a visual survey of the spectral data to identify concurrent DAM radio arcs, from May 5, 2016, through September, 2017 (Cassini’s end-of-mission). We found six events for which two or more observers clearly captured the same group of arcs. In one of the events on December 3, 2016, Juno first captured a group of the DAM arcs around 4:00 UT and two intense arcs were later recorded in NDA spectrograms at 6:30 and 7:45 UT. On the same day from 13:44 to 14:24 UT, the Hubble Space Telescope (HST) observed a bright auroral arc at ultraviolet wavelengths with an emitted power of 20 to 25 GW, suggesting a possible link to the concurrently observed DAM arcs. In this paper, we show results from the stereoscopic DAM radio observations and compare with the ultraviolet auroras captured by HST