Human factor XIa (FXIa) is a serine protease in the intrinsic coagulation pathway. FXIa has been actively targeted to develop new anticoagulants that are associated with a reduced risk of bleeding. Thousands of FXIa inhibitors have been reported, yet none has reached the clinic thus far. We describe here a novel class of sulfonated molecules that allosterically inhibit FXIa with moderate potency. A library of 18 sulfonated molecules was evaluated for the inhibition of FXIa using a chromogenic substrate hydrolysis assay. Only six molecules inhibited FXIa with IC50 values of 4.6–29.5 μM. Michaelis–Menten kinetics indicated that sulfonated molecules are allosteric inhibitors of FXIa. Inhibition of FXIa by these molecules was reversed by protamine. The molecules also showed moderate anticoagulant effects in human plasma with preference to prolong activated partial thromboplastin time. Their binding to an allosteric site in the catalytic domain of FXIa was modeled to illustrate potential binding mode and potential important Arg/Lys residues. Particularly, inhibitor 16 (IC50 = 4.6 µM) demonstrated good selectivity over a panel of serine proteases including those in the coagulation process. Inhibitor 16 did not significantly compromise the viability of three cell lines. Overall, the reported sulfonated molecules serve as a new platform to design selective, potent, and allosteric inhibitors of FXIa for therapeutic applications.
Background The increased risk of loss to follow-up among TB smokers raises concern over the secondary spread within the community. This study aimed to determine the factors associated with loss to follow-up among TB patients who smoke. Methods All registered TB patients who smoke in the state of Selangor between 2013 and 2017 via the Malaysian Tuberculosis Information System (MyTB) database were included for analysis. TB patients who smoke were considered those who are “current smoker” during the notification, while loss to follow-up was defined as a TB patient who had interrupted treatment for 2 months or longer. There were 3 main variable domains included for analysis: sociodemographic profiles, disease profiles, and comorbidities. Logistic regression analysis was used to identify determinants of loss to follow-up among TB patients who smoke. Results A total of 14.1% (N = 813) of TB patients who smoke loss to follow-up. The determinants of loss to follow-up among TB smokers were working age population aged 32-41 and 42-53 years old (AOR 1.08; 95%CI 1.23,2.08) and (AOR 1.44; 95%CI 1.11,1.87) respectively, Malaysian nationality (AOR 2.34; 95%CI 1.66,3.30), patients staying in urban area (AOR 1.55; 95% CI 1.23,1.97), income level less than RM2160 (AOR 1.59; 95% CI 1.14,2.20), un-employed (AOR 1.30; 95%CI 1.09-1.55), have low education level i.e., secondary school education, primary school education and no formal education (AOR 1.60; 95%CI 1.22,2.10), (AOR 1.73; 95%CI 1.16,2.57) and (AOR 2.29; 95% CI 1.57,3.33) respectively, previously treated TB cases (AOR 2.19; 95% CI 1.71,2.81), active TB case detection methods (AOR 2.06; 95%CI 1.40,3.02), moderate lesion x-ray (AOR 1.60; 95%CI 1.13,2.27) and HIV positive (AOR 1.36; 95%CI 1.02,1.82). All the significant factors gave rise to the final model of determinants, with a predictability of 67.2% (95% CI 65.0,69.3). Conclusions The high proportion of loss to follow-up among TB patients who smoke highlight the importance of providing early risk detection that examines the three main domains of risk factors such as socioeconomic, disease profiles and comorbidities. Potential integrated intervention should aim to reduce the proportion of smoking among TB patients through the stop smoking programme together with directly observed therapy (DOT).
Donating blood is a noble act that serves a humanitarian cause. This study aims to explore the barriers from donating blood amongst non-donors. Four focus group discussions (FGD) were conducted amongst non-blood donors. The discussions were carried out in the local language, and the verbatim was translated into English. Most of the participants were aware of the importance of donating blood to save other people. Fear is the most factors that hinders them from becoming a blood donor. The participants recommended the use of advertisements that could stir an emotional reaction. Blood banks should hence organise more blood donation campaigns to spread the awareness in the community.Keywords: awareness; blood donation; blood bank; focus group discussioneISSN: 2398-4287 © 2019. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.DOI: https://doi.org/10.21834/e-bpj.v4i10.1622
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.