Refining reproduction number estimates to account for unobserved generations of infection in emerging epidemics

Background: Estimating the transmissibility of infectious diseases is key to inform situational awareness and for response planning. Several methods tend to overestimate the basic (R0) and effective (Rt) reproduction numbers during the initial phases of an epidemic. The reasons driving the observed bias are unknown. In this work we explore the impact of incomplete observations and underreporting of the first generations of infections during the initial epidemic phase. Methods: We propose a debiasing procedure which utilises a linear exponential growth model to infer unobserved initial generations of infections and apply it to EpiEstim. We assess the performance of our adjustment using simulated data, considering different levels of transmissibility and reporting rates. We also apply the proposed correction to SARS-CoV-2 incidence data reported in Italy, Sweden, the United Kingdom and the United States of America. Results: In all simulation scenarios, our adjustment outperforms the original EpiEstim method. The proposed correction reduces the systematic bias and the quantification of uncertainty is more precise, as better coverage of the true R0 values is achieved with tighter credible intervals. When applied to real world data, the proposed adjustment produces basic reproduction number estimates which closely match the estimates obtained in other studies while making use of a minimal amount of data. Conclusions: The proposed adjustment refines the reproduction number estimates obtained with the current EpiEstim implementation by producing improved, more precise estimates earlier than with the original method. This has relevant public health implications

Evaluation of Major Minerals and Trace Elements in Wild and Domesticated Edible Herbs Traditionally Used in the Mediterranean Area

The human diet is characterized by the intake of major minerals (Na, K, Ca, Mg, P, N) and trace elements (Zn, Mn, Se, Cu, Fe, Co, I, Cr, F, Pb, Cd) for their key role in many metabolic functions. Nowadays, the research of sources able to improve their intake is in continuous evolution, especially in the undeveloped countries. In this sense, wild edible herbs, commonly used since ancient times, can represent a good alternative to improve the daily human intake of minerals. In this study, four wild edible species, Rumex acetosa, Picris hieracioides, Cichorium intybus, and Plantago coronopus, were analyzed for their content in Na, K, Ca, Mg, Cu, Mn, Fe, and Zn and, besides, three domestications (named “soilless,” pot, and open field) were evaluated in the analyzed species in the prospective of their commercialization as valuable sources of minerals in the human diet. Nitrate and oxalate contents were also evaluated, given their negative impact on human health. Results unveil that open field domestication allowed the plants to maintain the content of major minerals similar to those measured in wild plants, especially in C. intybus and P. hieracioides. The trace elements Cu, Mn, Fe, and Zn were not recorded at high content irrespectively to the wild collection or domestications. Finally, plants grown in the open field also accounted for a high oxalate and nitrate content, especially in R. acetosa. Further researches should be aimed at decreasing the oxalate and nitrate content in the domesticated species and to promote the commercialization of the domesticated species

Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy.

Abstract Extracellular vesicles (EVs) that are derived from mesenchymal stromal cells (MSCs) have been shown to reprogram injured cells by activating regenerative processes. We herein investigate the potential therapeutic effect of EVs, shed by human bone marrow MSCs and by human liver stem-like cells (HLSCs), on the progression and reversion of fibrosis in a mouse model of diabetic nephropathy, as induced by streptozotocin. After the development of nephropathy, stem cell-derived EVs were administered weekly to diabetic mice for four weeks. The stem cell-derived EV treatment, but not the fibroblast EV treatment that was used as a control, significantly ameliorated functional parameters, such as albumin/creatinine excretion, plasma creatinine and blood urea nitrogen, which are altered in diabetic mice. Moreover, the renal fibrosis that develops during diabetic nephropathy progression was significantly inhibited in stem cell EV-treated animals. A correlation was found between the down regulation of several pro-fibrotic genes in renal tissues and the anti-fibrotic effect of HLSC and MSC EVs. A comparative analysis of HLSC and MSC EV miRNA content highlighted some common and some specific patterns of miRNAs that target predicted pro-fibrotic genes. In conclusion, stem cell-derived EVs inhibit fibrosis and prevent its progression in a model of diabetes-induced chronic kidney injury

CONVERGENCE OF SIGNALING BY INTERLEUKIN-3, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, AND MAST CELL GROWTH FACTOR ON JAK2 TYROSINE KINASE

Mast cell growth factor (MGF) (also called stem cell factor) synergizes with several lymphokines, including interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), to promote proliferation and differentiation of certain hemopoietic progenitor cells. Although similar patterns of tyrosine-phosphorylated proteins characterize cells stimulated by MGF, IL-3, and GM-CSF, only the MGF receptor is a tyrosine kinase, and the heterodimeric receptors for IL-3 and GM-CSF share a common beta subunit that is devoid of enzymatic activity. Here we show that signaling pathways utilized by all three cytokines include the cytoplasmic tyrosine kinase JAK2. Analysis of several factor-dependent myeloid cell lines indicated that JAK2 is physically associated with the common beta subunit and with MGF receptor (c-Kit) even prior to ligand binding. However, each of the ligands induced elevated tyrosine phosphorylation of JAK2 and a consequent increase in its catalytic activity. These results demonstrate for the first time the convergence within the same myeloid cells of signaling pathways originating in two distinct lymphokine receptors and a tyrosine kinase receptor on activation of a cytoplasmic tyrosine kinase