Remdesivir is a nucleoside analog approved by the US FDA for treatment of COVID-19. Here, we present a 3.9-Å-resolution cryo-EM reconstruction of a remdesivir-stalled RNA-dependent RNA polymerase complex, revealing full incorporation of 3 copies of remdesivir monophosphate (RMP) and a partially incorporated fourth RMP in the active site. The structure reveals that RMP blocks RNA translocation after incorporation of 3 bases following RMP, resulting in delayed chain termination, which can guide the rational design of improved antiviral drugs.
  Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but has inherent risks. Microbial Ecosystem Therapeutic 2 (MET-2) is an oral encapsulated formulation of 40 lyophilised bacterial species initially isolated from stool of a healthy donor, but subsequently manufactured independently of donors, eliminating potential risks introduced by changes in donor health.  https://www.selleckchem.com/products/gsk484-hcl.html  The aim of this study was to determine MET-2 activity, safety, and tolerability.
 
  This phase 1, open-label, single-group feasibility study was done in Alberta, Canada. The main inclusion criteria were mild to moderate C difficile infection and at least one episode of C difficile infection recurrence (ie, two episodes of C difficile infection) within 12 months. Initial daily treatment was ten oral capsules for 2 days, then three capsules for 8 days. If C difficile infection recurred, a higher dose was offered 20 capsules for 2 days, then three capsules for 8 days. Patients were followed for advertients after initial treatment, increasing to 18 (95%) 40 days after retreatment. No mortality associated with C difficile infection, infections associated with MET-2 treatment, or other serious adverse events were observed. The most common self-limited, mild to moderate symptoms reported during treatment were diarrhoea in 12 (63%) of 19 patients and abdominal cramps in 12 (63%). After MET-2 treatment, quality of life improved significantly, as did alpha diversity in stool microbial composition (p=1·93×10
  ). MET-2 associated taxa were found in greater abundance in most patients after treatment compared with baseline. 16 (84%) of 19 patients did not have recurrence of C difficile infection by day 130.
 
  MET-2 appears to be safe, efficacious, and well tolerated among patients with recurrent C difficile infection. Results must be validated in controlled studies.
 
  NuBiyota.
 NuBiyota.
  Transgender people are disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide, and culturally competent prevention and treatment services are often unavailable or inaccessible. Despite recent improvements in national HIV responses for many key populations in east Africa, evidence of effective responses informed by transgender sexual health needs is sparse. We aimed to assess gender identity among men and transgender people who have sex with men in Kenya, and to explore its associations with sexual health-related outcomes, risk behaviours, and uptake of HIV prevention and care interventions.
 
  We did a cross-sectional study in Nairobi, Kenya, and recruited adult cisgender men and transfeminine people who reported having sex with men, through respondent-driven sampling. Inclusion criteria were possession of a valid study coupon, being aged 18 years or older, having male sex assignment at birth or male gender identification currently, living within 50 km of Nairobi, and hin the past 12 months. Use of pre-exposure prophylaxis and post-exposure prophylaxis was low in both groups.
 
  Transfeminine people who have sex with men have a higher burden of HIV and associated risk behaviours compared with cisgender MSM in the same context, yet their uptake of prevention and care services is poor. Policies should acknowledge the specific needs of transfeminine people as distinct from cisgender MSM, and support health-care providers to address these needs.
 
  Evidence for HIV Prevention in Southern Africa (EHPSA), UK Aid.
 Evidence for HIV Prevention in Southern Africa (EHPSA), UK Aid.Adherence to non-pharmaceutical interventions to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been highly variable across settings, particularly in the USA. In this Personal View, we review data supporting the importance of the viral inoculum (the dose of viral particles from an infected source over time) in increasing the probability of infection in respiratory, gastrointestinal, and sexually transmitted viral infections in humans. We also review the available evidence linking the relationship of the viral inoculum to disease severity. Non-pharmaceutical interventions might reduce the susceptibility to SARS-CoV-2 infection by reducing the viral inoculum when there is exposure to an infectious source. Data from physical sciences research suggest that masks protect the wearer by filtering virus from external sources, and others by reducing expulsion of virus by the wearer. Social distancing, handwashing, and improved ventilation also reduce the exposure amount of viral particles from an infectious source. Maintaining and increasing non-pharmaceutical interventions can help to quell SARS-CoV-2 as we enter the second year of the pandemic. Finally, we argue that even as safe and effective vaccines are being rolled out, non-pharmaceutical interventions will continue to play an essential role in suppressing SARS-CoV-2 transmission until equitable and widespread vaccine administration has been completed.Humans occupy a wider range of environments, process more energy, and have greater biomass than any other species because we are able to culturally evolve complex, locally adaptive technologies.1 Competing models make different predictions about the role of causal knowledge in this process. Some argue that innovation and transmission cannot occur without causal understanding,2-5 while others posit that complex technologies can evolve without causal understanding.1,6-10 Prior research on this topic has been restricted to theoretical work and experimental studies with student participants.11-13 The Hadza are foragers who rely on bows for subsistence.14-16 We interviewed skilled Hadza bowyers (bow-makers) and compared their beliefs regarding the tradeoffs in bow construction to those revealed by experimental and engineering research. If bowyers understand the tradeoffs, it is plausible that cultural evolution is rooted in causal understanding, while if they do not, the cultural accumulation of knowledge is likely more important in the process.