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Background: The X-linked bleeding disorder hemophilia B, caused by mutation(s) in the coagulation factor (F)IX gene, leads to partial or total loss of its function, requiring lifelong FIX replacement therapy. Although new recombinant FIX (rIX) therapeutics like albumin fusion proteins (rIX-FP) enable longer plasma half-life and thus less frequent administration, the complexity of intravenous (i.v.) injection remains., Objectives: The study aimed to characterize rIX-FP variants with anticipated enhanced specific activity, which would leverage rIX-FP's superior pharmacokinetic profile with beneficial characteristics for subcutaneous (s.c.) administration., Methods: Two rIX-FP variants, R338L ("Padua variant") and R338L/E410K, were characterized in vitro. Pharmacokinetic profiles of FIX antigen and activity levels were evaluated in FIX-deficient mice after i.v. and s.c. administration of these variants (dosing based on antigen levels). The efficacy of the most promising variant was tested after i.v. and s.c. administration (dosing based on activity) in a tail clip bleeding model. A marketed wild-type (WT) rIX-FP product served as the comparator., Results: Both rIX-FP variants showed a 4- to 5-fold increase in specific activity in vitro compared with rIX(WT)-FP, while FXIa-mediated activation was the fastest for rIX(WT)-FP and rIX(R338L)-FP. Compared with rIX(WT)-FP and rIX(R338L/E410K)-FP, rIX(R338L)-FP exhibited higher FIX activity exposure after i.v. and s.c. administration and demonstrated comparable efficacy with rIX(WT)-FP in reducing bleeding time and blood loss in FIX-deficient mice requiring ∼4 times lower protein amount., Conclusion: rIX(R338L)-FP was shown to be a promising candidate for s.c. administration, exhibiting increased specific activity combined with higher activity-based exposure and indicating efficacy at a lower protein dose., Competing Interests: Declaration of competing interests K.S. is a patient representative for one of CSL’s products. J.R., W.S.-B., P.P., P.C., M.W.N., and S.P. are employees of CSL Innovation GmbH. E.H. is an employee of CSL Behring LLC, and A.R.-S. is an employee of CSL Limited. Furthermore, M.W.N., S.P., E.H., and P.P. hold shares of CSL Limited., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The composition of the oral milieu reflects oral health. Saliva provides an environment for multiple microorganisms, and contains soluble factors and immune cells. Neutrophils, which rapidly react on the changes in the microenvironment, are a major immune cell population in saliva and thus may serve as a biomarker for oral pathologies. This review focuses on salivary neutrophils in the oral cavity, their phenotype changes in physiological and pathological conditions, as well as on factors regulating oral neutrophil amount, activation and functionality, with special emphasis on oral cancer and its risk factors., (Copyright © 2020 Domnich, Riedesel, Pylaeva, Kürten, Buer, Lang and Jablonska.)

Study Objective: Human papillomavirus (HPV) vaccines will soon be available for clinical use, and the effectiveness of vaccine delivery programs will depend largely upon whether providers recommend the vaccine. The objectives of this study were to examine family physicians' attitudes about HPV immunization and to identify predictors of intention to recommend immunization., Design: Cross-sectional survey instrument assessing provider and practice characteristics, knowledge about HPV, attitudes about HPV vaccination, and intention to administer two hypothetical HPV vaccines., Participants: Surveys were mailed to a national random sample of 1,000 American Academy of Family Physicians (AAFP) members., Main Outcome Measure: Intention to administer two hypothetical HPV vaccines (a cervical cancer/genital wart vaccine and a cervical cancer vaccine) to boys and girls of different ages., Results: One hundred fifty-five surveys (15.5%) were returned and 145 were used in the final sample. Participants reported higher intention to recommend both hypothetical HPV vaccines to girls vs. boys (P < 0.0001) and to older vs. younger adolescents (P < 0.0001). They were more likely to recommend a cervical cancer/genital wart vaccine than a cervical cancer vaccine to boys and girls (P < 0.001). Variables independently associated with intention (P < 0.05) included: female gender of provider, knowledge about HPV, belief that organizations such as the AAFP would endorse vaccination, and fewer perceived barriers to vaccination., Conclusions: Female gender, knowledge about HPV, and attitudes about vaccination were independently associated with family physicians' intention to recommend HPV vaccines. Vaccination initiatives directed toward family physicians should focus on modifiable predictors of intention to vaccinate, such as HPV knowledge and attitudes about vaccination.

Objective: Soluble thrombomodulin (sTM), a proposed serum marker of endothelial cell injury, was investigated as a parameter of disease activity in patients with systemic lupus erythematosus (SLE)., Methods: Levels of sTM were determined by enzyme-linked immunosorbent assay. Disease activity was assessed using 3 established scoring systems: the American College of Rheumatology (ACR), the New York Hospital for Special Surgery (NYHSS), and the Systemic Lupus Activity Measure (SLAM) systems., Results: A close correlation was found between sTM levels and disease activity as assessed with all 3 scoring systems: r = 0.52 by the ACR, 0.75 by the NYHSS, and 0.82 by the SLAM., Conclusion: We found that sTM is a sensitive serologic marker of organ involvement in patients with SLE. Furthermore, sTM may prove to be an important marker for vasculitis in general.