Estimation of Abbreviated Cyclosporine A Area under the Concentration-Time Curve in Allogenic Stem Cell Transplantation after Oral Administration

Measurements of Cyclosporine (CsA) systemic exposure permit its dose adjustment in allogenic stem cell transplantation recipients to prevent graft-versus-host disease. CsA LSSs were developed and validated from 60 ASCT patients via multiple linear regressions. All whole-blood samples were analyzed by fluorescence polarization immunoassay (FPIA-Axym). The 10 models that have used CsA concentrations at a single time point did not have a good fit with AUC0–12 (R2 < 0.90). C2 and C4 were the time points that correlated best with AUC0–12 h, R2 were respectively 0.848, and 0.897. The LSS equation with the best predictive performance (bias, precision and number of samples) utilized three sampling concentrations was AUC0–12 h = 0.607 + 1.569 × C0.5 + 2.098 × C2 + 3.603 × C4 (R2 = 0.943). Optimal LSSs equations which limited to those utilizing three timed concentrations taken within 4 hours post-dose developed from ASCT recipient's patients yielded a low bias <5% ranged from 1.27% to 2.68% and good precision <15% ranged from 9.60% and 11.02%. We propose an LSS model with equation AUC0–12 h = 0.82 + 2.766 × C2 + 3.409 × C4 for a practical reason. Bias and precision for this model are respectively 2.68% and 11.02%

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Facial Hyperpigmentation during Imatinib Therapy for Gastrointestinal Stromal Tumor

We report a rare case of facial hyperpigmentation during imatinib therapy for a gastrointestinal stromal tumor

Hypericum Humifusum Leaves Attenuates Hepatic Ischemia-Reperfusion Injury in a Rat Model

Introduction. Effective prevention strategies require specific actions during the different phases of ischemia-reperfusion (I-R) injury. The objective of our study is to evaluate the effect of aqueous extract of Hypericum humifusum leaves (HHL) on liver I-R model in Rat.Material and methods. Animals were subjected to 90 min of hepatic ischemia followed by reperfusion (120 min). HHL extract (25 mg/mL/kg) was injected 15 min before reperfusion. To evaluate the effect of HHL extract on I-R, we have monitored transaminases levels, Malondialdehyde (MDA) concentration, histological lesions (apoptosis and necrosis) and compared the results to a reference oxidant vitamin E.Results. The determination of total phenol extracts of HHL was 59.91 ± 0.35 mg of Gallic Acid/g dry plant material with higher antioxidant activity (91.73% ± 1.67) compared to vitamin E (87.42%). Using aqueous extract of HHL, we noted a significant decrease of AST and ALT [1129 UI (585/1995) and 768 UI (335/1375)] compared to no-treated group [5,585.5 UI (5,035/12,070) and 8,099.5 UI (5,040/12,326)] as a decrease in MDA content [85.7% protection (50.9/91.5)]. HHL extract reduce the damage induced by I-R of 48.7% (27/48.7) and 96.1% (95.7/96.5) for necrosis and apoptosis lesions respectively.Conclusion. HHL aqueous extract have potential to protect liver from the damage effect induced by I-R better than vitamin E solution