Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.

The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088.

Comparison of two alternative sequences with cabazitaxel and 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: A retrospective multicenter study (LuCaS).

Background: Cabazitaxel and Lu-PSMA-617 have been shown to improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and androgen receptor pathway inhibitors (ARPI). we aimed to evaluate the impact of sequencing cabazitaxel and Lu-PSMA-617 on survival outcomes in patients with mCRPC.

Patients And Methods: This is a retrospective, multicenter, cohort study which included patients with mCRPC who received sequential treatment with Lu-PSMA-617 and cabazitaxel between January 2015 and December 2023.

Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223: a post hoc analysis of the REASSURE study.

Background: Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (Ra) treatment, but their association with treatment outcomes is unclear.

Methods: For patients with metastatic castration-resistant prostate cancer treated with Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2).

Environmental Dissemination of SARS-CoV-2: An Analysis Employing Crassphage and Next-Generation Sequencing Protocols.

This study aimed to investigate the dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in water samples obtained during the coronavirus disease 2019 pandemic period, employing cross-assembly phage (crAssphage) as a fecal contamination biomarker and next-generation sequencing protocols to characterize SARS-CoV-2 variants. Raw wastewater and surface water (stream and sea) samples were collected for over a month in Rio de Janeiro, Brazil. Ultracentrifugation and negatively charged membrane filtration were employed for viral concentration of the wastewater and surface water samples, respectively.

Genomics-based timely detection of dengue virus type I genotypes I and V in Uruguay.

This study details a genomics-based approach for the early detection of mosquito-borne pathogens, marked by Uruguay's first ever complete genomic sequencing of Dengue Virus type I genotypes I and V. This pioneering effort has facilitated the prompt identification of these genotypes within the country, enabling Uruguayan public health authorities to develop timely and effective response strategies. Further integrated into this approach is a climate-driven suitability measure, closely associated with Dengue case reports and indicative of the local climate's role in the virus's transmission in the country within the changing climate context.