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Introduction: The high recombinogenic potential of HIV-1 has resulted in the generation of countless unique recombinant forms (URFs) and around 120 reported circulating recombinant forms (CRFs). Here we identify through analyses of near full-length genomes (NFLG) a new HIV-1 CRF derived from subtypes B and F1., Methods: HIV-1 protease-reverse transcriptase (Pr-RT) sequences were obtained by RT-PCR amplification from plasma RNA. Near full-length genome sequences were obtained after amplification by RT-PCR in 5 overlapping fragments. Phylogenetic sequence analyses were performed via maximum likelihood. Mosaic structures were analyzed by bootscanning and phylogenetic analyses of genome segments. Temporal and geographical estimations of clade emergence were performed with a Bayesian coalescent method., Results: Through phylogenetic analyses of HIV-1 Pr-RT sequences obtained by us from samples collected in Spain and downloaded from databases, we identified a BF1 recombinant cluster segregating from previously reported CRFs comprising 52 viruses, most from Brazil ( n = 26), Spain ( n = 11), and Italy ( n = 9). The analyses of NFLG genomes of 4 viruses of the cluster, 2 from Spain and 2 from Italy, allowed to identify a new CRF, designated CRF75_BF1, which exhibits a complex mosaic structure with 20 breakpoints. All 4 patients harboring CRF75_BF1 viruses studied by us had CD4 + T-cell lymphocyte counts below 220/mm 3 less than one year after diagnosis, a proportion significantly higher ( p = 0.0074) than the 29% found in other patients studied in Spain by us during the same period. The origin of the clade comprising CRF75_BF1 and related viruses was estimated around 1984 in Brazil, with subsequent introduction of CRF75_BF1 in Italy around 1992, and migration from Italy to Spain around 1999., Conclusion: A new HIV-1 CRF, designated CRF75_BF1, has been identified. CRF75_BF1 is the 6th CRF of South American origin initially identified in Western Europe, reflecting the increasing relationship of South American and European HIV-1 epidemics. The finding of low CD4 + T-cell lymphocyte counts early after diagnosis in patients harboring CRF75_BF1 viruses warrants further investigation on the virulence of this variant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bacqué, Delgado, Gil, Ibarra, Benito, García-Arata, Moreno-Lorenzo, Sáez de Adana, Gómez-González, Sánchez, Montero and Thomson.)

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina ( n = 4), Spain ( n = 3), Paraguay ( n = 1), Brazil ( n = 1), and Italy ( n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17 gag , integrase, gp120, gp41- rev overlap, and nef , which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF "family" clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bacqué, Delgado, Benito, Moreno-Lorenzo, Montero, Gil, Sánchez, Nieto-Toboso, Muñoz, Zubero-Sulibarria, Ugalde, García-Bodas, Cañada, del Romero, Rodríguez, Rodríguez-Avial, Elorduy-Otazua, Portu, García-Costa, Ocampo, Cabrera and Thomson.)

Introduction: Emergency medical regulation is a risky activity. In France, emergency medical societies have proposed activity and performance indicators, but their lists are non-exhaustive, unstructured and used heterogeneously among emergency medical call centres (Centres de Réception et de Régulation des Appels, CRRA). Our objective was to build by means of regional stakeholder consensus an operational quality dashboard for CRRAs., Methods: We conducted an observational step in a French CRRA from June to September 2018 and at the same time listed existing activity and quality indicators through a rapid international literature review. We adapted and classified all indicators identified in a structured table. We prioritised them from April to September 2019 by seeking consensus with one regulator physician and one medical regulation assistant from the 13 CRRAs of the largest French region. We used an adapted Delphi method with a prioritisation scale from 1 to 9., Results: The rapid review of literature included 33 studies among the 414 identified and, with the first observational step, resulted in a list of 360 quality indicators covering the following areas: material resources, human resources, quality approach, call handling and postcall support. 15 of the 26 members participated in the entire process. Seventy indicators were considered as priorities with strong agreement among participants. We built an operational dashboard of quality indicators deemed high priority and provided 70 descriptive indicator sheets., Conclusion: Our study allowed to build an operational quality dashboard for CRRAs as a ready-to-use support for an internal audit, for prioritisation of quality approach actions and for national and international benchmarking., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

HIV-1 protease-reverse transcriptase sequences from 62 HIV-1-infected individuals recently diagnosed in Moscow were analyzed. Subtype A former Soviet Union (FSU) (A FSU ) variant was the predominant clade (62.9%), followed by subtype B (22.6%), unique recombinants (6.5%), subtype G (6.5%), and CRF01_AE (1.6%). A FSU predominated among people who inject drugs (88.9%) and heterosexually acquired infections (77.8%), while subtype B was the most prevalent genetic form among men who have sex with men (44%), although A FSU was also frequent in this population (36%). Forty-eight (77.4%) viruses branched within intrasubtype clusters, three of which, of subtype B, had a majority of viruses collected outside of FSU. The four subtype G viruses identified in this study belonged to the Portuguese-Spanish (Iberian) variant and, together with three from databases, formed a Russian cluster closely related to viruses from Denmark. This is the first report of the circulation of the Iberian subtype G variant in Russia.

Human recombinant basic fibroblast growth factor (bFGF) is a potent mitogen for normal human dermal fibroblasts in the presence of heparin which binds to and stabilizes it. The optimal mitotic response is obtained with a concentration of 1 ng/ml of bFGF in monolayer cultures (non-differentiated fibroblasts) as well as in the better-differentiated fibroblasts obtained through the 'collagen lattices' culture system (fibroblasts embedded in a 3-dimensional collagen gel) achieving a doubling of the cell number in 8 days. Despite increasing the number of cells, bFGF decreases the ability of fibroblasts to contract collagen fibers. This inhibition is concentration-dependent and reaches a plateau at a dose of about 1 ng/ml. This effect is associated with a bFGF-induced decrease of fibroblast volume. Various dosing regimens indicate that although the highest response was obtained by daily dosing nearly optimal response was obtained either by early daily dosing or short intermittent treatment. Interestingly, the fibroblast mitotic response to bFGF decreases steadily when fibroblasts mature in collagen gels. The mitogenic properties of bFGF associated to its ability to inhibit fibroblasts contraction, if demonstrated in vivo, may be of interest in the management of wound healing.