56 research outputs found

    Molecular characterization of Streptococcus pyogenes (StrepA) non-invasive isolates during the 2022–2023 UK upsurge

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    At the end of 2022 into early 2023, the UK Health Security Agency reported unusually high levels of scarlet fever and invasive disease caused by Streptococcus pyogenes (StrepA or group A Streptococcus). During this time, we collected and genome-sequenced 341 non-invasive throat and skin S. pyogenes isolates identified during routine clinical diagnostic testing in Sheffield, a large UK city. We compared the data with that obtained from a similar collection of 165 isolates from 2016 to 2017. Numbers of throat-associated isolates collected peaked in early December 2022, reflecting the national scarlet fever upsurge, while skin infections peaked later in December. The most common emm-types in 2022–2023 were emm1 (28.7 %), emm12 (24.9 %) and emm22 (7.7 %) in throat and emm1 (22 %), emm12 (10 %), emm76 (18 %) and emm49 (7 %) in skin. While all emm1 isolates were the M1UK lineage, the comparison with 2016–2017 revealed diverse lineages in other emm-types, including emm12, and emergent lineages within other types including a new acapsular emm75 lineage, demonstrating that the upsurge was not completely driven by a single genotype. The analysis of the capsule locus predicted that only 51 % of throat isolates would produce capsule compared with 78% of skin isolates. Ninety per cent of throat isolates were also predicted to have high NADase and streptolysin O (SLO) expression, based on the promoter sequence, compared with only 56% of skin isolates. Our study has highlighted the value in analysis of non-invasive isolates to characterize tissue tropisms, as well as changing strain diversity and emerging genomic features which may have implications for spillover into invasive disease and future S. pyogenes upsurges

    A patient-derived explant (PDE) model of hormone-dependent cancer

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    Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.Margaret M. Centenera, Theresa E. Hickey, Shalini Jindal, Natalie K. Ryan, Preethi Ravindranathan, Hisham Mohammed, Jessica L. Robinson, Matthew J. Schiewer, Shihong Ma, Payal Kapur, Peter D. Sutherland, Clive E. Hoffmann, Claus G. Roehrborn, Leonard G. Gomella, Jason S. Carroll, Stephen N. Birrell, Karen E. Knudsen, Ganesh V. Raj, Lisa M. Butler, Wayne D. Tille

    Capim-elefante (Pennisetum purpureum Schum.), sob duas doses de nitrogênio. Consumo e produção de leite

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    A produção de leite, o consumo voluntário de matéria seca e a taxa de passagem da FDN no trato gastrintestinal em quatro épocas do ano (julho, outubro, janeiro e março), de vacas mestiças, sob pastejo de capim-elefante, submetido a dois níveis de nitrogênio (300 e 700 kg de N/ha•ano), foram estimados. Foi usado pastejo rotativo com três dias de ocupação e 30 de descanso, empregando-se 36 vacas lactantes mestiças Holandês x Zebu, em uma lotação de 6 vacas/ha. A estimativa de consumo e a taxa de passagem foram determinadas em apenas 24 animais. Para a coleta de extrusas, foram usadas duas vacas esôfago-fistuladas. O consumo foi estimado usando-se a relação produção fecal:indigestibilidade dos alimentos. A produção fecal foi estimada usando-se a FDN da extrusa marcada com dicromato de sódio fornecida em dose única. O consumo de MS total não foi influenciado pelas doses de N e por épocas do ano, com valores médios diários de 10,9 e 10,5 kg /MS•vaca para as doses de 300 e 700 kg N/ha•ano, respectivamente. Entretanto, o consumo de MS do capim-elefante foi influenciado por doses de N e épocas, com valores de 6,5 e 5,6 kg/vaca•dia para as doses de N supracitadas, respectivamente. O capim-elefante contribuiu com 26,0% da MS total ingerida, durante a época seca (julho/outubro) e sua contribuição aumentou para 84,0% na época das águas (janeiro/março). A produção diária de leite não foi influenciada por doses de N, com produções médias de 11,6 e 12,3 kg de leite/vaca•dia, para as doses de 300 e 700 kg N/ha•ano, respectivamente.The milk production, the dry matter intake (DMI) and the NDF passage rate in the gastrointestinal tract in four seasons (July, October, January and March), of crossbred cows, under grazing of elephant grass, submitted to two levels of nitrogen (300 and 700 kg N/ha•year) were estimated. The rotation grazing with three days of occupation and 30 days of resting, using 36 crossbred Holstein Zebu milking cows, in a stocking rate of 6 cows/ha, was used. The estimates of the intake and passage rate were determined only in 24 animals. For the extrusa collection, two esophageal fistulated cows were used. The intake was estimated using the fecal output: feed indigestibility ratio. The fecal output was estimated using the NDF of the extrusa marked with sodium dichromium fed in an unique dose. The total dry matter intake was not affected by the N levels and the year seasons, with average values of 10.9 and 10.5 kg DM/cow, for the levels of 300 and 700kg N/ha•year, respectively. However, the DM intake of the elephant grass was affected by N levels and year seasons, with reported values of 6.55 e 5.63 kg/cow•day, for the above described N levels, respectively. The elephant grass contributed with 26% of the total DM intake during the dry season (July/October) and its contribution increased up to 84% in the rainy season (January/March). The milk production was not affected by N levels, with reported average production of 11.6 and 12.3 kg/cow•day, for the levels of 300 and 700 kg N/ha•year, respectively
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