Trypanosoma brucei Glycogen Synthase Kinase-3, A Target for Anti-Trypanosomal Drug Development: A Public-Private Partnership to Identify Novel Leads

Over 60 million people in sub-Saharan Africa are at risk of infection with the parasite Trypanosoma brucei which causes Human African Trypanosomiasis (HAT), also known as sleeping sickness. The disease results in systemic and neurological disability to its victims. At present, only four drugs are available for treatment of HAT. However, these drugs are expensive, limited in efficacy and are severely toxic, hence the need to develop new therapies. Previously, the short TbruGSK-3 short has been validated as a potential target for developing new drugs against HAT. Because this enzyme has also been pursued as a drug target for other diseases, several inhibitors are available for screening against the parasite enzyme. Here we present the results of screening over 16,000 inhibitors of human GSK-3β (HsGSK-3) from the Pfizer compound collection against TbruGSK-3 short. The resulting active compounds were tested for selectivity versus HsGSK-3β and a panel of human kinases, as well as their ability to inhibit proliferation of the parasite in vitro. We have identified attractive compounds that now form potential starting points for drug discovery against HAT. This is an example of how a tripartite partnership involving pharmaceutical industries, academic institutions and non-government organisations such as WHO TDR, can stimulate research for neglected diseases

Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks

These authors contributed equally: Alpha K. Keita, Fara R. Koundouno, Martin Faye, Ariane Düx, Julia Hinzmann.International audienc

“Control-Alt-Delete”: Rebooting Solutions for the E-Waste Problem

A number of efforts have been launched to solve the global electronic waste (e-waste) problem. The efficiency of e-waste recycling is subject to variable national legislation, technical capacity, consumer participation, and even detoxification. E-waste management activities result in procedural irregularities and risk disparities across national boundaries. We review these variables to reveal opportunities for research and policy to reduce the risks from accumulating e-waste and ineffective recycling. Full regulation and consumer participation should be controlled and reinforced to improve local e-waste system. Aiming at standardizing best practice, we alter and identify modular recycling process and infrastructure in eco-industrial parks that will be expectantly effective in countries and regions to handle the similar e-waste stream. Toxicity can be deleted through material substitution and detoxification during the life cycle of electronics. Based on the idea of "Control-Alt-Delete", four patterns of the way forward for global e-waste recycling are proposed to meet a variety of local situations

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.[Background] Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants.[Methods] Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures.[Results] Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities.[Conclusion] This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu (2022-500385-99-00).EU-SolidAct is part of the European pandemic preparedness network EU RESPONSE, funded by the EU Horizon 2020 Research and Innovation programme, under grant number 101015736. EU-SolidAct has also received funding from CAPNET (France) and Klinbeforsk (Norway).Peer reviewe

A 32 GHz urban micro cell measurement campaign for 5G candidate spectrum region

International audienceA 32 GHz urban microcellular measurement campaign is presented in this paper. A path loss model in line-of-sight (LOS) for the fifth-generation (5G) candidate frequency band 31.8-33.4 GHz is provided, and different key channel metrics such as omni-directional path loss, angular and delay spreads and Rician K-factor are investigated. The investigation shows that no significant difference between the 28 GHz and 32 GHz frequency bands for the studied metrics. © 2017 Euraap

Severe malaria during pregnancy at the maternity ward of the municipal medical center of Ratoma, Guinea-Conakry

Background: Gestational malaria remains a major public health problem in malarious areas. The objectives of this work were to describe the socio-demographic, clinical, paraclinical, therapeutic and prognostic characteristics of patients who developed severe malaria during pregnancy.Methods: It was a descriptive prospective study carried out in the maternity ward of Ratoma municipal medical center, which was carried out over a period of 6 months from 01 October 2018 to 31 March 2019. This study involved all pregnant women who had presented severe malaria according to WHO criteria.Results: The incidence of severe malaria during pregnancy was 7%. The average age of our patients was 22.4 years with extremes of 15 and 47 years. The symptomatology that motivated the consultation was variable, the most frequent signs were: hyperthermia (100%), headache (79%), vomiting (99%). The general examination at admission objectified a fever with an average temperature of 39°C with extremes of 38-40.4°C. All patients had a positive rapid diagnostic test (RDT) as well as their thicker drop. The hemogram revealed the existence of a more or less severe anemia in 89.9% of cases. All patients were treated with parenteral quinine (100%). Maternal lethality was 1.8%. After severe malaria, 70 patients (62.5%) carried their pregnancy to term and 40 delivered an eutrophic child (35.71%), 30 (26.78%) delivered a hypotrophic child, 20 (17.85%) had a spontaneous abortion, premature delivery was observed in 10 patients (8.9%), and fetal death in utero was observed in 12 patients (10.71%).Conclusions: All patients had received parenteral quinine curative therapy. Maternal and perinatal complications were common. To improve this prognosis, intermittent preventive treatment and the use of insecticide-treated nets, which are the most effective prevention method at this time, must be further promoted in anticipation of the much hoped-for vaccine