A critical analysis of national plans for climate adaptation for health in South America.

Climate adaptation measures are critical for protecting human health. National Adaptation Plans (NAPs), Nationally Determined Contributions (NDCs), and National Communications (NCs) play a crucial role in helping countries identify, analyze, and address their vulnerabilities to climate change impacts, while also assessing available resources and capacities. This study aimed to assess the comprehensiveness of South American countries' NAPs, NDCs, and NCs in addressing the effects of climate change on health. A total of 38 NAPs, NDCs, and NCs of 12 South American countries were analysed. Ad hoc scores were developed to assess baseline information, adaptation proposals, identification of involved institutions, funding needs and allocation, measurable progress indicators, and coherence. Overall, all South American countries have NDCs and NCs, and seven have NAPs. In most countries, the intersectoral health analysis revealed a lack of linkage to health issues related to that sector. Additionally, most planning documents lack detailed information to guide policymakers in taking practical actions; areas with low scores include allocation of funds, involvement of health-related institutions, and measurable indicators. While South American countries acknowledge the health impacts of climate change in their plans, enhancing public health protection requires maximizing climate policy benefits and including health-related issues across all relevant sectors. Funding: This study was not funded. However, three co-authors received funding for some of their time: AV and KC were supported by the Wellcome Trust (209734/Z/17/Z); RCN was funded by K01AI139284 (NIH-NIAID). Funding for the publication was provided by Universidad Peruana Cayetano Heredia.

A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.

SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein.

Coronavirus disease-2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including precipitating cases of probable Parkinson's disease. As microglial NLRP3 inflammasome activation is a major driver of neurodegeneration, here we interrogated whether SARS-CoV-2 can promote microglial NLRP3 inflammasome activation. Using SARS-CoV-2 infection of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) as a COVID-19 pre-clinical model, we established the presence of virus in the brain together with microglial activation and NLRP3 inflammasome upregulation in comparison to uninfected mice. Next, utilising a model of human monocyte-derived microglia, we identified that SARS-CoV-2 isolates can bind and enter human microglia in the absence of viral replication. This interaction of virus and microglia directly induced robust inflammasome activation, even in the absence of another priming signal. Mechanistically, we demonstrated that purified SARS-CoV-2 spike glycoprotein activated the NLRP3 inflammasome in LPS-primed microglia, in a ACE2-dependent manner. Spike protein also could prime the inflammasome in microglia through NF-κB signalling, allowing for activation through either ATP, nigericin or α-synuclein. Notably, SARS-CoV-2 and spike protein-mediated microglial inflammasome activation was significantly enhanced in the presence of α-synuclein fibrils and was entirely ablated by NLRP3-inhibition. Finally, we demonstrate SARS-CoV-2 infected hACE2 mice treated orally post-infection with the NLRP3 inhibitory drug MCC950, have significantly reduced microglial inflammasome activation, and increased survival in comparison with untreated SARS-CoV-2 infected mice. These results support a possible mechanism of microglial innate immune activation by SARS-CoV-2, which could explain the increased vulnerability to developing neurological symptoms akin to Parkinson's disease in COVID-19 infected individuals, and a potential therapeutic avenue for intervention.

Potent neutralization of clinical isolates of SARS-CoV-2 D614 and G614 variants by a monomeric, sub-nanomolar affinity nanobody.

Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to reduce the burden placed on health systems, the situation remains critical. Effective diagnosis, treatment, and prophylactic measures are urgently required to meet global demand: recombinant antibodies fulfill these requirements and have marked clinical potential. Here, we describe the fast-tracked development of an alpaca Nanobody specific for the receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein with potential therapeutic applicability. We present a rapid method for nanobody isolation that includes an optimized immunization regimen coupled with VHH library E. coli surface display, which allows single-step selection of Nanobodies using a simple density gradient centrifugation of the bacterial library. The selected single and monomeric Nanobody, W25, binds to the SARS-CoV-2 S RBD with sub-nanomolar affinity and efficiently competes with ACE-2 receptor binding. Furthermore, W25 potently neutralizes SARS-CoV-2 wild type and the D614G variant with IC50 values in the nanomolar range, demonstrating its potential as antiviral agent.

[Evolution of Epiphysiodesis Surgery]. / Evolución de la Cirugía de Epifisiodesis.

INTRODUCTION: Surgical modulation of physeal growth, currently better known as "Guided Growth", is a procedure used as a treatment for length differences or axis alterations of the extremities. Although its use is increasing due to the development of new less invasive techniques, there are no statistical analyzes in the literature that support this. OBJECTIVE: To evaluate the incidence of the surgery codified as "Epi- physiodesis (Femur and/or Tibia)" in the Chilean population, from January 1st, 2010 to December 31, 2019, the days of hospital stay associated with that code and the demographic data of the analyzed po pulation. PATIENTS AND METHOD: We obtained from the Chilean Department of Statistics and Health Information (DEIS) database, all hospital discharges from January 1st, 2010 to December 31, 2019, from which we extracted the results with the code "Epiphysiodesis (Femur and/or Tibia)", in children under 15 years. The number of procedures per year, days of hospital stay, age, and sex were analyzed. RESULTS: In Chile, the number of procedures coded as "Epiphysiodesis (Femur and/or Tibia)" increa sed during the period analyzed. The days of hospital stay decreased progressively between 2012 and 2017. The procedure was performed mostly in women, and in the 5-9 years age group, showing an upward trend in children of the group of 10-14 years between 2015 and 2019. CONCLUSIONS: Further analysis must be carried out to determine the factors that produce these results, which are probably related to access to more efficient and simple techniques, with less morbidity.