A Generalized Mechano-Pharmaco-Biological Model For Bone Remodeling Including Cortisol Variation

The process of bone remodeling requires a strict coordination of bone resorption and formation in time and space in order to maintain consistent bone quality and quantity. Bone-resorbing osteoclasts and bone-forming osteoblasts are the two major players in the remodeling process. Their coordination is achieved by generating the appropriate number of osteoblasts since osteoblastic-lineage cells govern the bone mass variation and regulate a corresponding number of osteoclasts. Furthermore, diverse hormones, cytokines and growth factors that strongly link osteoblasts to osteoclasts coordinated these two cell populations. The understanding of this complex remodeling process and predicting its evolution is crucial to manage bone strength under physiologic and pathologic conditions. Several mathematical models have been suggested to clarify this remodeling process, from the earliest purely phenomenological to the latest biomechanical and mechanobiological models. In this current article, a general mathematical model is proposed to fill the gaps identified in former bone remodeling models. The proposed model is the result of combining existing bone remodeling models to present an updated model, which also incorporates several important parameters affecting bone remodeling under various physiologic and pathologic conditions. Furthermore, the proposed model can be extended to include additional parameters in the future. These parameters are divided into four groups according to their origin, whether endogenous or exogenous, and the cell population they affect, whether osteoclasts or osteoblasts. The model also enables easy coupling of biological models to pharmacological and/or mechanical models in the future. (c) 2021 by the authors. Licensee MDPI, Basel, Switzerland

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

Isolation and molecular characterisation of Mycobacterium bovis from raw milk in Tunisia

Background: Consumption of raw milk and unpasteurized dairy products is common in Tunisia where bovine tuberculosis remains enzootic. We herein investigated the frequency of M. bovis isolation from raw milk. Methods: Three hundred and six milk samples collected from 102 infected cows in different Tunisian regions were analysed. M. bovis isolates were further characterized by spoligotyping and variable number tandem repeat typing. Results: A total of five (4.9 %) M. bovis strains exhibiting three different genotypes were isolated. Conclusion: This study demonstrates that consumers of raw milk or derivatives in Tunisia are at high risk of zoonotic infection with M. bovis

SUPERPAVE design mixture performance evaluation using Epolene modifier for cold semi-arid climatic region of Saudi Arabia

Purpose: To evaluate the superpave design performance using Epolene (EE-2) as modifier, since SUPERPAVE design is a modified and sophisticated aspect as compared to previous mix design for asphalt mixtures. This is primarily due to the fact that superpave design mix also takes into consideration properties of materials beside asphalt. Design/methodology/approach: This study was conducted using Epolene (EE-2) as modifier in order to evaluate the performance of SUPERPAVE suitability for construction of roads in Alfaraa campus (King Khalid University) Abha, in Asir Province of Saudi Arabia. Glow number test, dynamic modulus test and indirect tensile strength test were conducted to evaluate the performance of EE-2 modifier against the control mixture. Findings: The mixture modified with EE-2 gave better performance in terms of temperature-based performance and resistance to moisture damage. Also, larger values of E*/sinφ were obtained for EE-2 modified mixture at various loading frequencies and temperature in comparison to control mixture. Research limitations/implications: The Epolene modifier successfully enhances and improves the SUPERPAVE mixture performance. Further studies are required to evaluate the performance of EE-2 modifier at much lower temperature ranges. Practical implications: The results of the study allow us to recommend the investigated asphalt mixture for applied for the construction of roads in the Alfaraa (new campus of King Khalid University), Abha, Asir province, Saudi Arabia. Originality/value: A modified asphalt mixture has been proposed that has better performance at higher and lower temperatures. The developed asphalt mixture is more resistant to moisture damage than the compared to control mixture