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Favipiravir (FVP) and remdesivir (RDV) have demonstrable antiviral activity against SARS-CoV-2. Here, the efficacy of FVP, RDV, and FVP with RDV (FVP + RDV) in combination was assessed in Syrian golden hamsters challenged with SARS-CoV- 2 (B.1.1.7) following intraperitoneal administration. At day 4 post infection, viral RNA and viral antigen expression were significantly lower in lungs for all three treatment groups compared to the sham treatment. Similarly, viral titres in the lungs were lower in all treatment groups compared to the sham treatment. The FVP + RDV combination was the only treatment group where viral RNA in nasal turbinate and lung, virus titres in lung, and viral antigen expression (lung) were all lower than those for the sham treatment group. Moreover, lower viral titre values were observed in the FVP + RDV group compared to other treatment groups, albeit only significantly lower in comparison to those in the RDV-only-treated group. Further assessment of the potential utility of FVP in combination with RDV may be warranted. Future studies should also consider whether the combination of these two drugs may reduce the speed at which drug resistance mutations are selected.

Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower in throat swabs in FVP (day 7), RDV (day 3, 5, 7), and RDV+PIB (day 3, 5) treatment groups. Similarly, findings were evident for nasal turbinate after PIB and RDV treatment, and lungs after PIB, FVP, and FVP+PIB treatment at day 7. Lung viral RNA levels after RDV and RDV+PIB treatment were only detectable in two animals per group, but the overall difference was not statistically significant. In situ examination of the lungs confirmed SARS-CoV-2 infection in all animals, except for one in each of the RDV and RDV+PIB treatment groups, which tested negative in all virus detection approaches. Overall, prevention of transmission was observed in most animals treated with RDV, while other agents reduced the viral load following contact transmission. No benefit of combining FVP or RDV with PIB was observed.

The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (p = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (p = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection.

Long-acting injectable (LAI) formulations promise to deliver patient benefits by overcoming issues associated with non-adherence. A preclinical assessment of semi-solid prodrug nanoparticle (SSPN) LAI formulations of emtricitabine (FTC) is reported here. Pharmacokinetics over 28 days were assessed in Wistar rats, New Zealand white rabbits, and Balb/C mice following intramuscular injection. Two lead formulations were assessed for the prevention of an HIV infection in NSG-cmah−/− humanised mice to ensure antiviral activities were as anticipated according to the pharmacokinetics. Cmax was reached by 12, 48, and 24 h in rats, rabbits, and mice, respectively. Plasma concentrations were below the limit of detection (2 ng/mL) by 21 days in rats and rabbits, and 28 days in mice. Mice treated with SSPN formulations demonstrated undetectable viral loads (700 copies/mL detection limit), and HIV RNA remained undetectable 28 days post-infection in plasma, spleen, lung, and liver. The in vivo data presented here demonstrate that the combined prodrug/SSPN approach can provide a dramatically extended pharmacokinetic half-life across multiple preclinical species. Species differences in renal clearance of FTC mean that longer exposures are likely to be achievable in humans than in preclinical models.

Through a social scientific lens, this paper considers the risk perceptions and “risk-based decision-making” of two key groups in a northern Tanzanian context: (1) frontline government meat inspectors and health officers charged with ensuring that red meat sold commercially is safe for people to consume, and (2) the workers who slaughter and process cattle and red meat prior to its sale in rural butcheries. In contrast to techno-scientific understandings of disease risk and “rational” approaches to its management, this paper foregrounds the role of social, economic and institutional context in shaping the perceptions and practices around meat safety of these actors whose daily, close proximity to meat means they play a significant role in mitigating potential meat-borne disease. We show how limited resources, and a combination of scientific and local knowledge and norms result in “situated expertise” and particular forms of risk perception and practice which both enhance and compromise meat safety in different ways. Actors' shared concerns with what is visible, ensures that visibly unsafe or abnormal meat is excluded from sale, and that infrastructure and meat is kept “clean” and free of certain visible contaminants such as soil or, on occasion, feces. While such contaminants serve as a good proxy for pathogen presence, meat inspectors and especially slaughter workers were much less aware of or concerned with invisible pathogens that may compromise meat safety. The role of process and meat handling did not figure very strongly in their concerns. Microorganisms such as Salmonella and Campylobacter, which can easily be transferred onto meat and persist in slaughter and meat sale environments, went unacknowledged. Although health officers expressed more concern with hygiene and meat handling, their influence over slaughter process and butchery operations was unclear. Ultimately, recognizing the perceptions and practices of frontline actors who engage with meat, and the ways in which social, material and institutional realities shape these, is important for understanding how decisions about risk and meat safety are made in the complexity and context of everyday life, and thus for finding effective ways to support them to further enhance their work.

El final de la guerra fría parecía prometer el final de una praxis geopolítica basada sobre la exclusión de la diferencia. Los teóricos hablaron de fluidez, hibridación y de un mundo en el que progresivamente disminuían las fronteras. Sin embargo, las consecuencias del 11 de septiembre mostraron claramente la persistencia de imágenes de un mundo peligroso donde el mantenimiento de las fronteras es vital para la seguridad. Mientras que este artículo se centrará inicialmente en la crítica de textos y de escritos de la geopolítica de la «guerra contra el terror» en el espíritu de una «geopolítica crítica», proseguirá hacia el planteamiento de una geopolítica feminista que ponga cuerpos y prácticas cotidianas en el centro de la geopolítica.

Repeat expansion diseases, including fragile X syndrome, Huntington’s disease, and C9orf72-related motor neuron disease and frontotemporal dementia, are a group of disorders associated with polymorphic expansions of tandem repeat nucleotide sequences. These expansions are highly repetitive and often hundreds to thousands of repeats in length, making accurate identification and determination of repeat length via PCR or sequencing challenging. Here we describe a protocol for monitoring repeat length in Drosophila models carrying 1,000 repeat C9orf72-related dipeptide repeat transgenes using Southern blotting. This protocol has been used regularly to check the length of these lines for over 100 generations with robust and repeatable results and can be implemented for monitoring any repeat expansion in Drosophila.

Abstract The effects of climate change on tropical forests may have global consequences due to the forests’ high biodiversity and major role in the global carbon cycle. In this study, we document the effects of experimental warming on the abundance and composition of a tropical forest floor herbaceous plant community in the Luquillo Experimental Forest, Puerto Rico. This study was conducted within Tropical Responses to Altered Climate Experiment (TRACE) plots, which use infrared heaters under free‐air, open‐field conditions, to warm understory vegetation and soils + 4°C above nearby control plots. Hurricanes Irma and María damaged the heating infrastructure in the second year of warming, therefore, the study included one pretreatment year, one year of warming, and one year of hurricane response with no warming. We measured percent leaf cover of individual herbaceous species, fern population dynamics, and species richness and diversity within three warmed and three control plots. Results showed that one year of experimental warming did not significantly affect the cover of individual herbaceous species, fern population dynamics, species richness, or species diversity. In contrast, herbaceous cover increased from 20% to 70%, bare ground decreased from 70% to 6%, and species composition shifted pre to posthurricane. The negligible effects of warming may have been due to the short duration of the warming treatment or an understory that is somewhat resistant to higher temperatures. Our results suggest that climate extremes that are predicted to increase with climate change, such as hurricanes and droughts, may cause more abrupt changes in tropical forest understories than longer‐term sustained warming.

Background It is preferable that children and adolescents requiring in-patient care for mental health problems are managed in age-appropriate facilities. To achieve this, nine specialist Child and Adolescent Mental Health Services (CAMHS) in-patient units have been commissioned in New South Wales (NSW) since 2002. Aims To examine trends in child and adolescent in-patient admissions since the opening of these CAMHS units. Method Analysis of separation data for under 18-year-olds to CAMHS, adult mental health and paediatric units for the period 2002 to 2013 in NSW, comparing districts with and without specialist CAMHS units. Results Separations from CAMHS, adult and paediatric units rose with time, but there was no interaction between time and health district type (with/without CAMHS unit). Five of eight health districts experienced increased separations of under 18-year-olds from adult units in the year of opening a CAMHS unit. Separations from related paediatric units increased in three of seven health districts. Conclusions Opening CAMHS units may be followed by a temporary increase in separations of young people from adult units, but it does not influence the flow of patients to non-CAMHS facilities in the longer term.