SARS-CoV-2 variants, spike mutations and immune escape.

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of 'variants of concern', that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets

Comparative Performance of Private and Public Healthcare Systems in Low- and Middle-Income Countries: A Systematic Review

A systematic review conducted by Sanjay Basu and colleagues reevaluates the evidence relating to comparative performance of public versus private sector healthcare delivery in low- and middle-income countries

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Intervenções de enfermagem relacionadas à promoção da saúde em portadores de hipertensão Intervenciones de enfermería relacionadas a la promoción de la salud en portadores de hipertensión Nursing interventions related to health promotion in hypertensive patients

OBJETIVOS: Identificar as competências de promoção da saúde em intervenções de enfermagem em portadores de hipertensão arterial. MÉTODOS: Seguiu-se a metodologia de revisão integrativa da literatura, utilizando as oito competências para a prática de promoção da saúde definidas na Conferência de Galway. Foram analisados 16 artigos. RESULTADOS: Os domínios de competência para a prática de promoção da saúde mais evidenciados foram Catalisar mudanças, Avaliação das necessidades e Parcerias. Apenas um artigo mencionou o uso das taxonomias de enfermagem para o planejamento da assistência em portadores de hipertensão arterial. CONCLUSÃO: Os resultados deste estudo poderão subsidiar as competências dos enfermeiros para a prática da promoção da saúde em portadores de hipertensão arterial.<br>OBJETIVOS: Identificar las competencias de promoción de la salud en intervenciones de enfermería en portadores de hipertensión arterial. MÉTODOS: Se siguió la metodología de La revisión integrativa de la literatura, utilizando las ocho competencias para la práctica de la promoción de la salud definidas en la Conferencia de Galway. Fueron analizados 16 artículos. RESULTADOS: Los dominios de competencia para la práctica de promoción de la salud más evidenciados fueron Catalizar cambios, Evaluación de las necesidades y sociedades. Sólo un artículo mencionó el uso de las taxonomías de enfermería para la planificación de la asistencia en portadores de hipertensión arterial. CONCLUSIÓN: Los resultados de este estudo pueden subsidiar las competencias de los enfermeros para la práctica de la promoción de la salud en portadores de hipertensión arterial.<br>OBJECTIVES: To identify the health promotion compentencies of nursing interventions for patient with hypertension. METHODS: The methodology of an integrative literature review was followed, using the eight competencies for the practice of health promotion that were defined at the Galway Consensus Conference. Sixteen articles were analyzed. RESULTS: The domains of competence for health promotion practice that were most evident were: catalyzing change, assessment of needs, and partnerships. Only one article mentioned the use of nursing taxonomies for planning care in patients with hypertension. CONCLUSION: The results of this study will support nursing competencies for practicing health promotion in patients with hypertension

Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex

Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. These short-lived protease complexes are formed through pro-convertases, which for the alternative pathway consist of the complement component C3b and the pro-enzyme factor B (FB). Here, we present the crystal structure at 2.2-Å resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. FB is loaded onto CVF through its pro-peptide Ba segment by specific contacts, which explain the specificity for the homologous C3b over the native C3 and inactive products iC3b and C3c. The protease segment Bb binds the carboxy terminus of CVF through the metal-ion dependent adhesion site of the Von Willebrand factor A-type domain. A possible dynamic equilibrium between a ‘loading' and ‘activation' state of the pro-convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. These insights into formation of convertases provide a basis for further development of complement therapeutics