Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

Can Diarylethene Photochromism Be Explained by a Reaction Path Alone? A CASSCF Study with Model MMVB Dynamics

The origin of the photochromic properties of diarylethenes is a conical intersection (which we have located computationally), but we show that dynamics calculations are necessary to explain why the conical intersection is accessible, because the excited-state reaction path is not contained in the branching space defining the intersection. Four different systems have been studied: 1,2-di(3-furyl)ethene, 1,2-di(3-thienyl)ethene, 1,2-bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene, and a model hydrocarbon system. Critical points on the ground- and excited-state potential energy surfaces were calculated using complete active space self-consistent field (CASSCF) theory; dynamics calculations were carried out using the molecular mechanics-valence bond (MMVB) method. The main experimental observations (i.e., picosecond time domain, quantum yield, temperature dependence, and fluorescence) can be interpreted on the basis of our results

Long Range Charge Separation in a Ferrocene-(Zinc Porphyrin)-Naphthanenediimide Triad with 1,2,3-Triazole Linkers

New dyad and triad systems based on a zinc porphyrin (ZnP), a naphthalenediimide (NDI), and a ferrocene (Fc) as molecular components, linked by 1,2,3-triazole bridges, ZnP-NDI (3) and Fc-ZnP-NDI (4), have been synthesized. Their photophysical behavior has been investigated by both visible excitation of the ZnP chromophore and UV excitation of the NDI unit. Dyad 3 exhibits relatively inefficient quenching of the ZnP singlet excited state, slow charge separation and fast charge recombination processes. Excitation of the NDI chromophore, on the other hand, leads to charge separation by both singlet and triplet quenching pathways, with the singlet charge-separated (CS) state recombining in a sub-ns time scale, and the triplet CS state decaying in ca. 90 ns. In the triad system 4, primary formation of Fc-ZnP+-NDI− charge separated state is followed by a secondary hole shift process from ZnP to Fc. The product of the stepwise charge-separation, Fc+-ZnP-NDI−, undergoes recombination to the ground state, as expected for a long-range process, in a much longer time scale, 1.9 s. The charge separated states are always formed more efficiently upon NDI excitation than upon ZnP excitation. DFT calculations on a bridge-acceptor fragment show that the bridge is expected to mediate a fast donor-to-bridge-to-acceptor electron cascade following excitation of the acceptor. More generally, triazole bridges may behave asymmetrically with respect to photoinduced electron transfer in dyads, kinetically favoring hole-transfer pathways triggered by excitation of the acceptor over electron-transfer pathways promoted by excitation of the donor

Long-Range Charge Separation in a Ferrocene-(zinc Porphyrin)-Naphtalenediimide Triad. Asymmetric Role of 1,2,3-Triazole Linkers

International audienceNew dyad and triad systems based on a zinc porphyrin (ZnP), a naphthalenediimide (NDI), and a ferrocene (Fc) as molecular components, linked by 1,2,3-triazole bridges, ZnP-NDI (3) and Fc-ZnP-NDI (4), have been synthesized. Their photophysical behavior has been investigated by both visible excitation of the ZnP chromophore and UV excitation of the NDI unit. Dyad 3 exhibits relatively inefficient quenching of the ZnP singlet excited state, slow charge separation, and fast charge recombination processes. Excitation of the NDI chromophore, on the other hand, leads to charge separation by both singlet and triplet quenching pathways, with the singlet charge-separated (CS) state recombining in a subnanosecond time scale and the triplet CS state decaying in ca. 90 ns. In the triad system 4, primary formation of the Fc-ZnP+-NDI- charge-separated state is followed by a secondary hole shift process from ZnP to Fc. The product of the stepwise charge separation, Fc+-ZnP-NDI-, undergoes recombination to the ground state in 1.9 μs. The charge-separated states are always formed more efficiently upon NDI excitation than upon ZnP excitation. DFT calculations on a bridge-acceptor fragment show that the bridge is expected to mediate a fast donor-to-bridge-to-acceptor electron cascade following excitation of the acceptor. More generally, triazole bridges may behave asymmetrically with respect to photoinduced electron transfer in dyads, kinetically favoring hole-transfer pathways triggered by excitation of the acceptor over electron-transfer pathways promoted by excitation of the donor

Electron Transfer Across Modular Oligo- p -phenylene Bridges in Ru(bpy) 2 (bpy–ph n –DQ) 4+ ( n = 1–5) Dyads. Unusual Effects of Bridge Elongation

International audienc

Long-Range Charge Separation in a Ferrocene–(Zinc Porphyrin)–Naphthalenediimide Triad. Asymmetric Role of 1,2,3-Triazole Linkers

New dyad and triad systems based on a zinc porphyrin (ZnP), a naphthalenediimide (NDI), and a ferrocene (Fc) as molecular components, linked by 1,2,3-triazole bridges, ZnP-NDI (<b>3</b>) and Fc-ZnP-NDI (<b>4</b>), have been synthesized. Their photophysical behavior has been investigated by both visible excitation of the ZnP chromophore and UV excitation of the NDI unit. Dyad <b>3</b> exhibits relatively inefficient quenching of the ZnP singlet excited state, slow charge separation, and fast charge recombination processes. Excitation of the NDI chromophore, on the other hand, leads to charge separation by both singlet and triplet quenching pathways, with the singlet charge-separated (CS) state recombining in a subnanosecond time scale and the triplet CS state decaying in ca. 90 ns. In the triad system <b>4</b>, primary formation of the Fc-ZnP⁺-NDI^– charge-separated state is followed by a secondary hole shift process from ZnP to Fc. The product of the stepwise charge separation, Fc⁺-ZnP-NDI^–, undergoes recombination to the ground state in 1.9 μs. The charge-separated states are always formed more efficiently upon NDI excitation than upon ZnP excitation. DFT calculations on a bridge–acceptor fragment show that the bridge is expected to mediate a fast donor-to-bridge-to-acceptor electron cascade following excitation of the acceptor. More generally, triazole bridges may behave asymmetrically with respect to photoinduced electron transfer in dyads, kinetically favoring hole-transfer pathways triggered by excitation of the acceptor over electron-transfer pathways promoted by excitation of the donor

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia

Background In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. Methods We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. Results Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24–0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12–0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). Conclusion In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.Peer reviewedFinal Published versio