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

Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: Potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells

The synthesis and potent inhibitory activity of novel 4-[(imidazol-1-yl and triazol-1-yl)(phenyl)methyl]aryl-and heteroaryl amines versus a MCF-7 CYP26A1 cell assay is described. Biaryl imidazole ([4-(imidazol-1-yl-phenyl-methyl)-phenyl]-naphthalen-2- yl-amine (8), IC50 = 0.5 lM; [4-(imidazol-1-yl-phenyl-methyl)-phenyl]-indan-5-yl-amine (9), IC50 = 1.0 lM) and heteroaryl imidazole derivatives ((1H-benzoimidazol-2-yl)-{4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (15), IC50 = 2.5 lM; benzooxazol-2-yl- {4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}-amine (16), IC50 = 0.9 lM; benzothiazol-2-yl-{4-[(5H-imidazol-1-yl)-phenyl-methyl]-phenyl}- amine (17), IC50 = 1.5 lM) were the most potent CYP26 inhibitors. Using a CYP26A1 homology model differences in activity were investigated. Incubation of SH-SY5Y human neuroblastoma cells with the imidazole aryl derivative 8, and the imidazole heteroaryl derivatives 16 and 17 potentiated the atRA-induced expression of CYP26B1. These data suggest that further structure– function studies leading to clinical development are warranted

Agostino. Dizionario enciclopedico,

Il \u201cDizionario enciclopedico\u201d presenta l\u2019opera, il pensiero e l\u2019influenza di di Agostino di Ippona. Fornisce un punto di partenza per rendere il pensiero di Agostino e la letteratura secondaria su di esso accessibili a lettori con diversi interessi e retroterra culturali. L\u2019opera raccoglie il lavoro di circa 150 studiosi i cui ambiti accademici includono gli studi umanistici, la storia, la filosofia, la scienza politica e la teologia. Essi provengono dall\u2019Europa, dal Nord America, dall\u2019Asia e dall\u2019Australia, ed hanno collaborato a realizzare i quasi 500 lemmi di cui consta l\u2019opera, fornendo una visione unitaria su molte questioni ed un\u2019adeguata bibliografia. L\u2019edizione italiana rappresenta la traduzione, revisione e correzione dell\u2019edizione americana, integrata con alcuni significativi lemmi, che non erano presenti nell\u2019edizione originale, come: agostinismo politico, Arendt, bellezza, Cartesio, croce, cuore, desiderio, Ecdicia, educazione, ermeneutica, fenomenologia, filosofia/teologia della storia, filosofia, Giansenismo, intenzionalit\ue0, Jaspers, linguaggio, mutabililit\ue0, notitia, partecipazione, Port Royal, rivelazione, schiavit\uf9, sequela, sessualit\ue0, speranza, spiritualismo cristiano, teologia, umilt\ue0, usura. Il nuovo impianto italiano \ue8 stato tenuto presente dall\u2019edizione francese, a cura di Marie-Anne Vannier (Cerf, Paris 2005

Technological readiness and implementation of genomic-driven precision medicine for complex diseases

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment – genomic-driven precision medicine (GDPM) – may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data

Combustion Measurements of Synthetic Fuels at Gas Turbine Conditions

Synthetic fuels are of interest as a replacement for aviation, diesel, and other petroleum-based fuels, and the present paper outlines a joint project to study the combustion behavior of Fischer-Tropsch (FT) synthetic fuels. To this end, shock-tube kinetics, shock-tube spray, and high-recirculation combustion rig experiments are being utilized to study the ignition delay times, chemical kinetics, and the formation of soot and emissions of FT jet fuels. The conditions for the present ignition delay times and CH* profiles ranged from 1391 to 1680 K with an average pressure of 2 atm and equivalence ratio of 1, highly diluted in argon. Undiluted experiments were conducted using a recently developed heterogeneous technique wherein the fuel is sprayed directly into the test region of a shock tube. The high recirculation combustion rig is a complete gas turbine where syntroleum was combusted and soot formation and particulates measured. Reduction of soot and emissions was observed, agreeing with previous investigations

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the \u201cDelirium Day\u201d study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors