This paper describes the process of planning for, and executing, the intervention and reports the initial results of its effect. Initial feedback indicated a positive response to the intervention. 9 out of 10 respondents (90%) rated their hospital experience with a maximum of five stars and all 10 respondents (100%) rated the psychosocial support materials with five stars. Doctors managing the patients also observed a reduction in the number of commonly asked questions following the deployment of the iPad.This quality improvement project is ongoing with plans for further research to determine how to better support the psychosocial needs of patients in isolation during a novel disease outbreak. This report is written based on the Standards for Quality Improvement Reporting Excellence guidelines.
  Syphilis rates among women in the USA more than doubled between 2014 and 2018. We sought to identify correlates of syphilis among women enrolled in the Women's Interagency HIV Study (WIHS) to inform targeted interventions.
 
  The retrospective cross-sectional analysis of secondary data included women with HIV or at-risk of HIV who enrolled in the multisite US WIHS cohort between 1994 and 2015. Syphilis screening was performed at baseline. Infection was defined serologically by a positive rapid plasma reagin test with confirmatory treponemal antibodies. Sociodemographic and behavioural characteristics stratified by baseline syphilis status were compared for women enrolled during early (1994-2002) and recent (2011-2015) years. Multivariable binomial modelling with backward selection (p>0.2 for removal) was used to model correlates of syphilis.
 
  The study included 3692 women in the early cohort and 1182 women in the recent cohort. Syphilis prevalence at enrolment was 7.5% and 3.7% in each cohort, respectively (p<0.01). In adjusted models for the early cohort, factors associated with syphilis included age, black race, low income, hepatitis C seropositivity, drug use, HIV infection and >100 lifetime sex partners (all p<0.05). In the recent cohort, age (adjusted prevalence OR (aPOR) 0.2, 95% CI 0.1 to 0.6 for 30-39 years; aPOR 0.5, 95% CI 0.2 to 1.0 for 40-49 years vs ≥50 years), hepatitis C seropositivity (aPOR 2.1, 95% CI 1.0 to 4.1) and problem alcohol use (aPOR 2.2, 95% CI 1.1 to 4.4) were associated with infection.
 
  Syphilis screening is critical for women with HIV and at-risk of HIV. Targeted prevention efforts should focus on women with hepatitis C and problem alcohol use.
 Syphilis screening is critical for women with HIV and at-risk of HIV. Targeted prevention efforts should focus on women with hepatitis C and problem alcohol use.The 3' to 5' exonuclease Pop2p (Caf1p) is part of the CCR4-NOT deadenylation complex that removes poly(A) tails from mRNAs in cells. Pop2p is structurally conserved in eukaryotes, but Saccharomyces cerevisiae Pop2p harbors noncanonical amino acids in its catalytic center. The enzymatic properties of S. cerevisiae Pop2p are not well defined. Here we characterize the RNA exonuclease activity of recombinant S. cerevisiae Pop2p. We find that S. cerevisiae Pop2p degrades RNAs via two alternative reactions pathways, one generating nucleotides with 5'-phosphates and RNA intermediates with 3'-hydroxyls, and the other generating nucleotides with 3'-phosphates and RNA intermediates with 3'-phosphates. The enzyme is not able to initiate the reaction on RNAs with a 3'-phosphate, which leads to accumulation of RNAs with 3'-phosphates that can exceed 10 nt and are resistant to further degradation by S. cerevisiae Pop2p. We further demonstrate that S.  https://www.selleckchem.com/products/Nolvadex.html  cerevisiae Pop2p degrades RNAs in three reaction phases an initial distributive phase, a second processive phase and a third phase during which processivity gradually declines. We also show that mutations of subsets of amino acids in the catalytic center, including those previously thought to inactivate the enzyme, moderately reduce, but not eliminate activity. Only mutation of all five amino acids in the catalytic center diminishes activity of Pop2p to background levels. Collectively, our results reveal robust exonuclease activity of S. cerevisiae Pop2p with unusual enzymatic properties, characterized by alternative degradation pathways, multiple reaction phases and functional redundancy of amino acids in the catalytic core.
  Hematopoietic progenitor kinase 1 (HPK1 or MAP4K1) has been demonstrated as a negative intracellular immune checkpoint in mediating antitumor immunity in studies with HPK1 knockout and kinase dead mice. Pharmacological inhibition of HPK1 is desirable to investigate the role of HPK1 in human immune cells with therapeutic implications. However, a significant challenge remains to identify a small molecule inhibitor of HPK1 with sufficient potency, selectivity, and other drug-like properties suitable for proof-of-concept studies. In this report, we identified a novel, potent, and selective HPK1 small molecule kinase inhibitor, compound K (CompK). A series of studies were conducted to investigate the mechanism of action of CompK, aiming to understand its potential application in cancer immunotherapy.
 
  Human primary T cells and dendritic cells (DCs) were investigated with CompK treatment under conditions relevant to tumor microenvironment (TME). Syngeneic tumor models were used to assess the in vivo pharmacologyddress cancer treatment resistance.
 CompK treatment significantly improved human T-cell functions, with enhanced TCR avidity to recognize TAAs and tumor cytolytic activity by CD8+ T cells. Additional benefits include DC maturation and priming facilitation in tumor draining lymph node. CompK represents a novel pharmacological agent to address cancer treatment resistance.
  Despite the remarkable benefits associated with the interventional treatment of melanomas (and other solid cancers) with immune checkpoint and Braf inhibitors (Brafi), most patients ultimately progress on therapy. The presence of multifocal/disseminated disease in patients increases their mortality risk. Hence, the development of novel strategies to effectively treat patients with melanomas that are resistant to anti-PD1 mAb (αPD1) and/or Brafi, particularly those with multifocal/disseminated disease remains a major unmet clinical need.
 
  Mice developing induced/spontaneous Braf
  /Pten
  melanomas were treated by cutaneous immunization with a DNA vaccine encoding the melanoma-associated antigen TRP2, with Brafi or αPD1 alone, or with a combination of these treatments. Tumor progression, tumor-infiltration by CD4
  and CD8
  T cells, and the development of TRP2-specific CD8
  T cells were then monitored over time.
 
  Vaccination led to durable antitumor immunity against PD1/Brafi-resistant melanomas in both single lesion and multifocal disease models, and it sensitized PD1-resistant melanomas to salvage therapy with αPD1.