Warm season precipitation climatology: first European results

International audienceTo date very low scores are associated to quantitative precipitation forecasts (QPF) of warm season precipitation, a fact mostly due to the little knowledge of the mechanisms driving these phenomena. The study aims to produce a five-year climatology (1999?2003) of warm season precipitation systems (MJJA) over Europe using Meteosat IR brightness temperatures as a contribution to a global study launched by the World Weather Research Programme (WWRP). Cold cloud persistence, span and duration of weather systems were determined to derive the zonal propagation speed and daily cycles

THE EFFICACY AND SAFETY OF PRAVASTATIN AND SIMVASTATIN IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA

The efficacy and safety of pravastatin, 10 mg once a day, were compared with that of simvastatin, 10 mg once a day, in 16 patients with primary type IIa hypercholesterolemia, in a nonrandomized, open-label, sequential trial of eight weeks. On both drug treatments significant reductions in total cholesterol (TC) (16.2% with pravastatin and 22.4% with simvastatin), low-density lipoprotein cholesterol (LDL-C) (26.3% with pravastatin and 31.4% with simvastatin), TC/high-density lipoprotein cholesterol (HDL-C) ratio (22.8% with pravastatin and 25.9% with simvastatin), and LDL-C/HDL-C ratio (22.9% with pravastatin and 25.0% with simvastatin) were observed at the eighth week. However, the reduction in TC and LDL-C appeared to be significantly (P < 0.05) greater after simvastatin treatment than with pravastatin. A statistically significant increase in HDL was achieved with pravastatin (11.4%) but not with simvastatin (2.9%). Serum triglyceride values increased with pravastatin (6.8%) and decreased with simvastatin (9.8%); these changes were not significant. With both drugs, at the end of the washout period, the plasma lipid levels returned to the pretreatment values. Both drugs were well tolerated and no serious side effects were observed

Orally available nucleoside analog UMM-766 provides protection in a murine model of orthopox disease

ABSTRACTAlthough smallpox has been eradicated, other orthopoxviruses continue to be a public health concern as exemplified by the ongoing Mpox (formerly monkeypox) global outbreak. While medical countermeasures (MCMs) previously approved by the Food and Drug Administration for the treatment of smallpox have been adopted for Mpox, previously described vulnerabilities coupled with the questionable benefit of at least one of the therapeutics during the 2022 Mpox outbreak reinforce the need for identifying and developing other MCMs against orthopoxviruses. Here, we screened a panel of Merck proprietary small molecules and identified a novel nucleoside inhibitor with potent broad-spectrum antiviral activity against multiple orthopoxviruses. Efficacy testing of a 7-day dosing regimen of the orally administered nucleoside in a murine model of severe orthopoxvirus infection yielded a dose-dependent increase in survival. Treated animals had greatly reduced lesions in the lung and nasal cavity, particularly in the 10 µg/mL dosing group. Viral levels were also markedly lower in the UMM-766-treated animals. This work demonstrates that this nucleoside analog has anti-orthopoxvirus efficacy and can protect against severe disease in a murine orthopox model.IMPORTANCEThe recent monkeypox virus pandemic demonstrates that members of the orthopoxvirus, which also includes variola virus, which causes smallpox, remain a public health issue. While currently FDA-approved treatment options exist, risks that resistant strains of orthopoxviruses may arise are a great concern. Thus, continued exploration of anti-poxvirus treatments is warranted. Here, we developed a template for a high-throughput screening assay to identify anti-poxvirus small-molecule drugs. By screening available drug libraries, we identified a compound that inhibited orthopoxvirus replication in cell culture. We then showed that this drug can protect animals against severe disease. Our findings here support the use of existing drug libraries to identify orthopoxvirus-targeting drugs that may serve as human-safe products to thwart future outbreaks