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Background Health care-associated infections during previous coronavirus epidemics involving severe acute respiratory syndrome and Middle East respiratory syndrome resulted from human-to-human transmission in hemodialysis (HD) facilities. The effect of a strategy of HD with cohort isolation-separate dialysis sessions for close contacts of patients with confirmed coronavirus disease 2019 (COVID-19)-on the prevention of secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in HD units is unknown. Methods Our multicenter cohort study of an HD with cohort isolation strategy enrolled close contacts of patients with confirmed COVID-19, including patients on HD and health care workers in HD units. Close contacts had been identified by epidemiologic investigation and tested negative on an immediate screening test for SARS-CoV-2. Results As of March 14, 11 patients on HD and 7 health care workers from 11 HD centers were diagnosed as having COVID-19. The immediate screening test was performed in 306 people, and among them, 302 close contacts with negative test results were enrolled. HD with cohort isolation was performed among all close contacts for a median of 14 days in seven centers. During cohort isolation, nine patients showed symptoms but tested negative for SARS-CoV-2. Two health care workers in the HD units (0.66% of the total group) were diagnosed at the termination test for SARS-CoV-2. Conclusions The transmission of COVID-19 can be controlled without closure of HD centers by implementing preemptive activities, including early detection with rapid testing, cohort isolation, collaboration between institutions, and continuous monitoring of infection. Our strategy and experience may provide helpful guidance for circumstances involving the rapid spread of infectious diseases such as COVID-19.Background Short-chain fatty acids derived from gut microbial fermentation of dietary fiber have been shown to suppress autoimmunity through mechanisms that include enhanced regulation by T regulatory cells (Tregs). Methods Using a murine kidney transplantation model, we examined the effects on alloimmunity of a high-fiber diet or supplementation with the short-chain fatty acid acetate. Kidney transplants were performed from BALB/c(H2d) to B6(H2b) mice as allografts in wild-type and recipient mice lacking the G protein-coupled receptor GPR43 (the metabolite-sensing receptor of acetate). Allograft mice received normal chow, a high-fiber diet, or normal chow supplemented with sodium acetate. We assessed rejection at days 14 (acute) and 100 (chronic), and used 16S rRNA sequencing to determine gut microbiota composition pretransplantation and post-transplantation. Results Wild-type mice fed normal chow exhibited dysbiosis after receiving a kidney allograft but not an isograft, despite the avoidance of antibiotics and immunosuppression for the latter. A high-fiber diet prevented dysbiosis in allograft recipients, who demonstrated prolonged survival and reduced evidence of rejection compared with mice fed normal chow. Allograft mice receiving supplemental sodium acetate exhibited similar protection from rejection, and subsequently demonstrated donor-specific tolerance. Depletion of CD25+ Tregs or absence of the short-chain fatty acid receptor GPR43 abolished this survival advantage. Selleckchem NVP-TAE684 Conclusions Manipulation of the microbiome by a high-fiber diet or supplementation with sodium acetate modified alloimmunity in a kidney transplant model, generating tolerance dependent on Tregs and GPR43. Diet-based therapy to induce changes in the gut microbiome can alter systemic alloimmunity in mice, in part through the production of short-chain fatty acids leading to Treg cell development, and merits study as a potential clinical strategy to facilitate transplant acceptance.Objectives As part of the International Cancer Benchmarking Partnership (ICBP) SURVMARK-2 project, we provide the most recent estimates of colon and rectal cancer survival in seven high-income countries by age and stage at diagnosis. Methods Data from 386 870 patients diagnosed during 2010-2014 from 19 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were analysed. 1-year and 5-year net survival from colon and rectal cancer were estimated by stage at diagnosis, age and country, RESULTS (One1-year) and 5-year net survival varied between (77.1% and 87.5%) 59.1% and 70.9% and (84.8% and 90.0%) 61.6% and 70.9% for colon and rectal cancer, respectively. Survival was consistently higher in Australia, Canada and Norway, with smaller proportions of patients with metastatic disease in Canada and Australia. International differences in (1-year) and 5-year survival were most pronounced for regional and distant colon cancer ranging between (86.0% and 94.1%) 62.5% and 77.5% and (40.7% and 56.4%) 8.0% and 17.3%, respectively. Similar patterns were observed for rectal cancer. Stage distribution of colon and rectal cancers by age varied across countries with marked survival differences for patients with metastatic disease and diagnosed at older ages (irrespective of stage). Conclusions Survival disparities for colon and rectal cancer across high-income countries are likely explained by earlier diagnosis in some countries and differences in treatment for regional and distant disease, as well as older age at diagnosis. Differences in cancer registration practice and different staging systems across countries may have impacted the comparisons.’Shock and kill’ therapeutic strategies towards HIV eradication are based on the transcriptional activation of latent HIV with a Latency-Reversing Agent (LRA), and the consequent killing of the reactivated cell by either the cytopathic effect of HIV or an arm of the immune system. We have recently found several benzotriazole and benzotriazine analogues that have the ability to reactivate latent HIV by inhibiting Signal Transducer and Activator of Transcription-5 (STAT5) SUMOylation and promoting STAT5 binding to the HIV LTR and increasing its transcriptional activity. To understand the essential structural groups required for biological activity of these molecules, we performed a systematic analysis of over 40 analogues. First, we characterized the essential motifs within these molecules that are required for their biological activity. Second, we identified three benzotriazine analogues with similar activity. We demonstrated that these three compounds are able to increase STAT5 phosphorylation and transcriptional activity.