A graph model of combination therapies

The simultaneous use of multiple medications causes drug–drug interactions (DDI) that impact therapeutic efficacy. Here, we argue that graph theory, in conjunction with game theory and ecosystem theory, can address this issue. We treat the coexistence of multiple drugs as a system in which DDI is modeled by game theory. We develop an ordinary differential equation model to characterize how the concentration of a drug changes as a result of its independent capacity and the dependent influence of other drugs through the metabolic response of the host. We coalesce all drugs into personalized and context-specific networks, which can reveal key DDI determinants of therapeutical efficacy. Our model can quantify drug synergy and antagonism and test the translational success of combination therapies to the clinic.     

Structured online training for university students to deliver peer-led addiction counselling for young drug abusers in China: Effect on improving knowledge,attitude, confidence,and skills

ObjectivesTo measure the effect of a structured online training programme on improving the knowledge, attitude, confidence, and skills of university students to deliver peer-led addiction counselling to young drug abusers.MethodsA structured training programme was designed for university students with a background in health-related disciplines. Pre- and post-training evaluations were conducted for 245 university students with health-related backgrounds who completed the training programme. The participants’ knowledge of and attitudes towards drug abuse and their confidence in delivering addiction counselling were evaluated and compared before and after the training. Counselling skills were assessed using a simulated standardised case.ResultsA paired test indicated that after attending the training programme, the participants’ knowledge of and attitudes towards drug abuse and their confidence in delivering addiction counselling were significantly improved. Most of the trained participants demonstrated satisfactory counselling skills.ConclusionParticipation in a one-day structured addiction training programme significantly improved students’ knowledge of and attitudes towards drug abuse and their confidence and skills to deliver addiction counselling.Practice implicationFuture research should elucidate the implementation of the counselling skills in terms of the counselling outcomes and successful referral. The clients’ health outcomes should be assessed to reflect the peer counsellors’ skills.     

Photocrosslinkable methacrylated gelatin hydrogel as a cell-friendly injectable delivery system for chlorhexidine in regenerative endodontics

ObjectivesThis work sought to formulate photocrosslinkable chlorhexidine (CHX)-laden methacrylated gelatin (CHX/GelMA) hydrogels with broad spectrum of action against endodontic pathogens as a clinically viable cell-friendly disinfection therapy prior to regenerative endodontics procedures.MethodsCHX/GelMA hydrogel formulations were successfully synthesized using CHX concentrations between 0.12 % and 5 % w/v. Hydrogel microstructure was evaluated by scanning electron microscopy (SEM). Swelling and enzymatic degradation were assessed to determine microenvironmental effects. Compression test was performed to investigate the influence of CHX incorporation on the hydrogels’ biomechanics. The antimicrobial and anti-biofilm potential of the formulated hydrogels were assessed using agar diffusion assays and a microcosms biofilm model, respectively. The cytocompatibility was evaluated by exposing stem cells from human exfoliated deciduous teeth (SHEDs) to hydrogel extracts (i.e., leachable byproducts obtained from overtime hydrogel incubation in phosphate buffer saline). The data were analyzed using One- and Two-way ANOVA and Tukey’s test (α = 0.05).ResultsCHX/GelMA hydrogels were effectively prepared. NMR spectroscopy confirmed the incorporation of CHX into GelMA. The addition of CHX did not change the micromorphology (pore size) nor the swelling profile (p > 0.05). CHX incorporation reduced the degradation rate of the hydrogels (p < 0.001); whereas, it contributed to increased compressive modulus (p < 0.05). Regarding the antimicrobial properties, the incorporation of CHX showed a statistically significant decrease in the number of bacteria colonies at 0.12 % and 0.5 % concentration (p < 0.001) and completely inhibited the growth of biofilm at concentration levels 1 %, 2 %, and 5 %. Meanwhile, the addition of CHX, regardless of the concentration, did not lead to cell toxicity, as cell viability values were above 70 %.SignificanceThe addition of CHX into GelMA showed significant antimicrobial action against the pathogens tested, even at low concentrations, with the potential to be used as a cell-friendly injectable drug delivery system for root canal disinfection prior to regenerative endodontics.     

医疗领域人工智能应用的研究进展＊

人工智能引发了医疗领域的数字革命，在推动行业发展方面具有极大潜力。本研究围绕临床诊疗、医学研究和公共卫生三个基本场景，聚焦人工智能与传统中医药的交叉与融合，并着重介绍人工智能在疾病诊断、决策支持、医学研究以及重大公共卫生事件中的应用。虽然人工智能在诸多方面显示出独特优势，但仍存在透明度不高、缺乏安全性评估和相关法律法规监管等问题需要谨慎解决，以促进人工智能技术在医疗领域的推广。     

BCL2 G quadruplex-binding small molecules: Current status and prospects for the development of next-generation anticancer therapeutics

B cell lymphoma 2 (BCL2) overexpression in a range of human tumors is often related to chemotherapy resistance and poor prognosis. GC-rich regions upstream of the P1 promoter in human BCL2 can form G-quadruplex (G4) structures through the stacking of four Hoogsteen-paired guanine bases. Stabilizing the G4 fold implies the inhibition of BCL2 expression and, thus, small molecules that selectively bind to the G4 are promising anticancer candidates. In this review, we discuss the structural aspects, binding affinity, selectivity, and biological activity of well-characterized BCL2 G4 binding ligands in vitro and in vivo. We also explore future directions in the research and development of G4-based anticancer therapeutics.     

Improving knowledge and trust in vaccines: A survey-based assessment of the potential of the European Union Clinical Trial Regulation No 536/2014 plain language summary to increase health literacy

The European Clinical Trial Regulation No 536/2014 is the first mandate for a non-technical, publicly disclosed, plain language summary (PLS) of clinical trial results. This easy-to-understand summary has the potential to inform the public about clinical trial results and thereby improve health literacy in vaccines.To investigate the utility of the PLS, we undertook 2 online surveys (July/October 2020) in the United Kingdom, the United States and India. Participants were selected by quota sampling to ensure representation of gender, age and parental status. Those lacking interest in vaccine clinical research were excluded. In survey 1, participants were questioned about their interest in and expectations of vaccine trial results. In survey 2, the perceptions of participants to a range of written communication styles used in publicly available PLSs were evaluated.A total of 66 (13%) and 122 (29%) individuals were excluded solely due to lack of interest in vaccine clinical research in surveys 1 and 2, respectively; 450 respondents (150/country) completed survey 1 and 300 (100/country) completed survey 2. In survey 1, there was a correlation (p < 0.01) between claimed knowledge of and trust in vaccines. Healthcare professionals were the most trusted source for vaccine information, while vaccine companies were ranked relatively low. In survey 2, infographic PLS formats were considered easiest to understand, most engaging and the strongest communicators. Emphasizing the main points of the infographics in the text did not improve comprehension or recall. Most respondents (86%) indicated that they would like to see this type of communication in the future.Overall, this research suggests that the PLS, by optimizing content and format, has a potential to increase health literacy, and thereby, as part of a wider integrated communication strategy, build vaccine knowledge and confidence.