Implementation of point-of-care testing of C-reactive protein concentrations to improve antibiotic targeting in respiratory illness in Vietnamese primary care: a pragmatic cluster-randomised controlled trial

Background In previous trials, point-of-care testing of C-reactive protein (CRP) concentrations safely reduced antibiotic use in non-severe acute respiratory infections in primary care. However, these trials were done in a research-oriented context with close support from research staff, which could have influenced prescribing practices. To better inform the potential for scaling up point-of-care testing of CRP in respiratory infections, we aimed to do a pragmatic trial of the intervention in a routine care setting. Methods We did a pragmatic, cluster-randomised controlled trial at 48 commune health centres in Viet Nam between June 1, 2020, and May 12, 2021. Eligible centres served populations of more than 3000 people, handled 10–40 respiratory infections per week, had licensed prescribers on site, and maintained electronic patient databases. Centres were randomly allocated (1:1) to provide point-of-care CRP testing plus routine care or routine care only. Randomisation was stratified by district and by baseline prescription level (ie, the proportion of patients with suspected acute respiratory infections to whom antibiotics were prescribed in 2019). Eligible patients were aged 1–65 years and visiting the commune health centre for a suspected acute respiratory infection with at least one focal sign or symptom and symptoms lasting less than 7 days. The primary endpoint was the proportion of patients prescribed an antibiotic at first attendance in the intention-to-treat population. The per-protocol analysis included only people who underwent CRP testing. Secondary safety outcomes included time to resolution of symptoms and frequency of hospitalisation. This trial is registered with ClinicalTrials.gov, NCT03855215. Findings 48 commune health centres were enrolled and randomly assigned, 24 to the intervention group (n=18 621 patients) and 24 to the control group (n=21 235). 17 345 (93·1%) patients in the intervention group were prescribed antibiotics, compared with 20 860 (98·2%) in the control group (adjusted relative risk 0·83 [95% CI 0·66–0·93]). Only 2606 (14%) of 18 621 patients in the intervention group underwent CRP testing and were included in the per-protocol analysis. When analyses were restricted to this population, larger reductions in prescribing were noted in the intervention group compared with the control group (adjusted relative risk 0·64 [95% CI 0·60–0·70]). Time to resolution of symptoms (hazard ratio 0·70 [95% CI 0·39–1·27]) and frequency of hospitalisation (nine in the intervention group vs 17 in the control group; adjusted relative risk 0·52 [95% CI 0·23–1·17]) did not differ between groups. Interpretation Use of point-of-care CRP testing efficaciously reduced prescription of antibiotics in patients with non-severe acute respiratory infections in primary health care in Viet Nam without compromising patient recovery. The low uptake of CRP testing suggests that barriers to implementation and compliance need to be addressed before scale-up of the intervention. Funding Australian Government, UK Government, and the Foundation for Innovative New Diagnostics

Bias-free solar hydrogen production at 19.8???mA???cm???2 using perovskite photocathode and lignocellulosic biomass

Solar hydrogen production is one of the ultimate technologies needed to realize a carbon-neutral, sustainable society. However, an energy-intensive water oxidation half-reaction together with the poor performance of conventional inorganic photocatalysts have been big hurdles for practical solar hydrogen production. Here we present a photoelectrochemical cell with a record high photocurrent density of 19.8???mA???cm???2 for hydrogen production by utilizing a high-performance organic???inorganic halide perovskite as a panchromatic absorber and lignocellulosic biomass as an alternative source of electrons working at lower potentials. In addition, value-added chemicals such as vanillin and acetovanillone are produced via the selective depolymerization of lignin in lignocellulosic biomass while cellulose remains close to intact for further utilization. This study paves the way to improve solar hydrogen productivity and simultaneously realize the effective use of lignocellulosic biomass

Lignin as a multifunctional photocatalyst for solar-powered biocatalytic oxyfunctionalization of C???H bonds

Each year, the pulp and paper industry produces approximately 50???million metric tons of lignin as waste, 95% of which is combusted or abandoned. Here, we report the use of lignin as a photocatalyst that forms H2O2 by O2 reduction and H2O oxidation under visible light. We investigated the photophysical and electronic properties of two lignin models, lignosulfonate and kraft lignin, by spectroscopic and photoelectrochemical analyses, and demonstrated the photoredox chemistry of lignin using these and other lignin models (for example, native-like cellulolytic enzyme lignin, artificial lignin dehydrogenation polymer and phenolic ??-aryl ether-type lignin dimer). Furthermore, the integration of lignin and H2O2-dependent unspecific peroxygenases (UPOs) enabled the highly enantioselective oxyfunctionalization of various C???H bonds. The use of lignin photocatalysts solves a number of the challenges relating to the sustainable activation of UPOs, notably, eliminating the need for artificial electron donors and suppressing the HO??-mediated inactivation of UPOs. Thus, the lignin???UPO hybrid catalyst achieved a total turnover number of UPO of 81,000 for solar-powered biocatalytic oxyfunctionalization in photochemical platforms

Anticoagulant Activity of Low-Molecular Weight Compounds from Heterometrus laoticus Scorpion Venom

Scorpion venoms are complex polypeptide mixtures, the ion channel blockers and antimicrobial peptides being the best studied components. The coagulopathic properties of scorpion venoms are poorly studied and the data about substances exhibiting these properties are very limited. During research on the Heterometrus laoticus scorpion venom, we have isolated low-molecular compounds with anticoagulant activity. Determination of their structure has shown that one of them is adenosine, and two others are dipeptides LeuTrp and IleTrp. The anticoagulant properties of adenosine, an inhibitor of platelet aggregation, are well known, but its presence in scorpion venom is shown for the first time. The dipeptides did not influence the coagulation time in standard plasma coagulation tests. However, similarly to adenosine, both peptides strongly prolonged the bleeding time from mouse tail and in vitro clot formation in whole blood. The dipeptides inhibited the secondary phase in platelet aggregation induced by ADP, and IleTrp decreased an initial rate of platelet aggregation induced by collagen. This suggests that their anticoagulant effects may be realized through the deterioration of platelet function. The ability of short peptides from venom to slow down blood coagulation and their presence in scorpion venom are established for the first time. Further studies are needed to elucidate the precise molecular mechanism of dipeptide anticoagulant activity

Phosphomolybdic Acid as a Catalyst for Oxidative Valorization of Biomass and Its Application as an Alternative Electron Source

Power- and solar-to-chemical energy conversion has been spotlighted as a promising technology for the efficient use of renewable energy resources. In principle, various chemicals can be sustainably produced through (photo)electrochemical reduction using water as a cheap and clean electron source. However, oxidation of water is a challenging task that results in low energy efficiency and reliability issues for the practical application of power- and solar-to-chemical energy conversion. Here, we show that various biomasses including lignin can be used as alternative electron sources. Electrons can be readily extracted from biomass using phosphomolybdic acid as a catalyst for oxidative depolymerization of biomass and an electron mediator at a much lower potential (0.95 V vs. reversible hydrogen electrode) than water using the best-performing but expensive catalysts (1.5-1.6 V). In particular, value-added chemicals such as CO and vanillin are produced as byproducts upon oxidative depolymerization of lignin. As a result, this approach allows efficient (photo)electrochemical production of hydrogen with a Faradaic efficiency close to unity at acidic pHs and brings additional economic benefits from byproducts

Recombinant lignin peroxidase with superior thermal stability and melanin decolorization efficiency in a typical human skin-mimicking environment

Recently, the desire for a safe and effective method for skin whitening has been growing in the cosmetics industry. Commonly used tyrosinase-inhibiting chemical reagents exhibit side effects. Thus, recent studies have focused on performing melanin decolorization with enzymes as an alternative due to the low toxicity of enzymes and their ability to decolorize melanin selectively. Herein, 10 different isozymes were expressed as recombinant lignin peroxidases (LiPs) from Phanerochaete chrysosporium (PcLiPs), and PcLiP isozyme 4 (PcLiP04) was selected due to its high stability and activity at pH 5.5 and 37 ??C, which is close to human skin conditions. In vitro melanin decolorization results indicated that PcLiP04 exhibited at least 2.9-fold higher efficiency than that of well-known lignin peroxidase (PcLiP01) in a typical human skin-mimicking environment. The interaction force between melanin films measured by a surface forces apparatus (SFA) revealed that the decolorization of melanin by PcLiP04 harbors a disrupted structure, possibly interrupting ??????? stacking and/or hydrogen bonds. In addition, a 3D reconstructed human pigmented epidermis skin model showed a decrease in melanin area to 59.8% using PcLiP04, which suggests that PcLiP04 exhibits a strong potential for skin whitening