Adrenomedullin Therapy for Moderate-to-Severe COVID-19 Pneumonia: Double-Blind Placebo-Controlled Phase 2a Trial

Adrenomedullin (AM) is a bioactive peptide that is strongly induced during severe inflammation, including pneumonia and sepsis, and serves as an organ-protective factor. The plasma concentration of AM is markedly increased in the novel coronavirus disease COVID-19 and is closely related to the severity of the disease and prognosis of patients. We performed two investigator-initiated trials to evaluate the efficacy and safety of AM in patients with moderate-to-severe COVID-19. This multicenter, double-blind, placebo-controlled phase-2a trial evaluated COVID-19 patients with severe (n = 33) and moderate (n = 31) pneumonia in Japan. Patients were randomly assigned to receive either 15 ng/kg/min AM or placebo. The primary endpoint was the duration of mechanical ventilation (MV) for severe pneumonia and oxygen support for moderate pneumonia. The main secondary endpoint was clinical status up to 30 days after the intervention. No differences in primary or secondary endpoints were observed between the AM and placebo groups in patients with severe or moderate pneumonia. In the severe pneumonia group, three patients in the placebo group died due to respiratory failure, and one patient in the AM group died due to respiratory failure. The respiratory function test at 30 days in the moderate pneumonia group tended to be better than that in the AM group and approached significance (p = 0.073). Although mild adverse events caused by the vasodilatory effects of AM were noted, the safety of AM for treating pneumonia was confirmed. In these trials, we did not observe a definitive efficacy of AM in moderate to severe pneumonia. Alternative strategies for the treatment of AM in pneumonia require further research

Observation of B+ → χc0K+

journal articl

Further characterization of carbonaceous materials in Hayabusa‐returned samples to understand their origin

Carbonaceous materials in the sample catcher of the Hayabusa spacecraft were assigned as category 3 particles. We investigated the category 3 particles with a suite of in situ microanalytical methods. Possible contaminants collected from the cleanrooms of the spacecraft assembly and extraterrestrial sample curation center (ESCuC) were also analyzed in the same manner as category 3 particles for comparison. Our data were integrated with those of the preliminary examination team for category 3 particles. Possible origins for the category 3 particles include contamination before and after the operation of the Hayabusa spacecraft.This is the peer reviewed version of the following article: "Further characterization of carbonaceous materials in Hayabusa‐returned samples to understand their origin", which has been published in final form at [https://doi.org/10.1111/maps.13236]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.journal articl

Phenolic Glycosides with Antimalarial Activity from <i>Grevillea</i> “Poorinda Queen”

In search of new antimalarial compounds, three new phenolic glycosides, robustasides E (1), F (2), and G (3), in addition to the known compounds robustaside D (4) and quercetin-7-O-[α-l-rhamnopyranosyl(1→6)-β-d-galactopyranoside] (5), were identified during chemical investigations of the MeOH extract from the leaves and twigs of Grevillea “Poorinda Queen”. The chemical structures of the new compounds were elucidated through 2D NMR spectroscopy, while the absolute configuration of the sugar was elucidated through chemical degradation and comparison with an authentic standard. Discussed in detail are the isolation and structure elucidation of 1−3, as well as the associated in vitro anitmalarial activities for 1−5. Also discussed are the in vivo anitmalarial and in vitro cytotoxic activities for 1, 3, and 4

Characteristics of the study populations at Dak Buk So, Dak Ngo and Quang Truc communes, Tuy Duc district, Dak Nong province, Central Highlands of Vietnam.

Characteristics of the study populations at Dak Buk So, Dak Ngo and Quang Truc communes, Tuy Duc district, Dak Nong province, Central Highlands of Vietnam.</p

MOESM3 of Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam

Additional file 3: Table S1. Adverse events before and after treatment of Vietnamese patients with AS + DHA–PPQ or AM–LUM for uncomplicated falciparum malaria

MOESM5 of Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam

Additional file 5: Table S1. Adverse events before and after treatment of Vietnamese patients with CQ for uncomplicated vivax malaria

RT-qPCR positive sample (asymptomatic malaria) prevalence in participants of different age groups in Dak Buk So, Dak Ngo and Quang Truc communes, Tuy Duc district, Dak Nong province, Central Vietnam in 2018–2019.

RT-qPCR positive sample (asymptomatic malaria) prevalence in participants of different age groups in Dak Buk So, Dak Ngo and Quang Truc communes, Tuy Duc district, Dak Nong province, Central Vietnam in 2018–2019.</p

S3 Appendix -

(XLSX)</p

Study sites of three communes in Tuy Duc district, Dak Nong province, Vietnam.

Custom map produced using MapInfo Professional v15.0.2 (Pitney Bowes Software Inc. 2015, Stamford, CT; https://www.pitneybowes.com) Geographic Information System (GIS) mapping software.</p