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。     

Factors Associated with Universal Free School Meal Provision Adoption among US Public Schools

BackgroundThe Community Eligibility Provision (CEP) allows high-poverty schools participating in US Department of Agriculture meal programs to offer universal free school meals. Emerging evidence suggests benefits of CEP for student meal participation, behavior, and academic performance. Although CEP became available nationwide in 2014, in school year 2019–2020, one third of eligible schools were not participating.ObjectiveThis study evaluates which school, district, and state factors are associated with CEP participation.DesignCross-sectional study comparing CEP-participating with eligible nonparticipating schools to assess the relationship between CEP participation and school, district, and state factors.ParticipantsUS public schools eligible for CEP in school year 2017–2018 (n = 42,813).Main Outcome MeasuresCEP participation.Statistical Analyses PerformedPenalized regression variable selection methods to determine which factors contribute information to the model. Generalized logistic regression to predict odds of CEP participation unadjusted and adjusted for each factor in the full sample and in stratified analyses by whether a state was part of the CEP phase-in period (early vs late implementing states).ResultsIn the full sample, adjusted odds of CEP participation were greater in states where CEP had been available longer (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.34, 1.67). In late implementing states, adjusted odds of CEP participation were higher in schools with more students directly certified for free meals (OR in schools with 80%–89% vs 30%–39% directly certified: 19.32; 95% CI, 12.98, 28.76), Title I schools (OR, 1.85; 95% CI, 1.55, 2.21), and urban schools (OR suburban vs urban, 0.46; 95% CI, 0.36, 0.59). Differences by school level, enrollment, district size, student race/ethnicity, and geographic region also existed.ConclusionsFindings may help advocates, state agencies, and policymakers understand potential barriers to adoption and guide research exploring effective strategies to promote uptake. Future research should use qualitative and longitudinal designs to explore barriers to adoption, including cost and state and local policies.     

The success of Australia’s ‘No Jab,No Pay’ policy at a local level; retrospective clinical audit of a single medical practice assessing incidence of catch-up vaccinations

Vaccination is a vital health care initiative to prevent individual and population infection. To increase vaccination rates the federal government implemented the ‘No Jab, No Pay’ policy, where eligibility for several government benefits required children to be fully vaccinated by removing ‘conscientious objections’ and expanding the age range of children whose families receive benefits. This study assesses the impact of this policy at a local area within a single medical practice community in NSW, Australia. A retrospective clinical audit was performed between 2012 and 2017 on a single general practice's vaccination records for children ≤19 years. Catch-up vaccinations were assessed based on age at vaccination. Incidence of catch-up vaccinations was assessed for each of four years before and two years after the implementation of the ‘No Jab, No Pay’ policy in January 2016, along with the age of children and vaccination(s) given. Catch-up vaccinations were assessed temporally either side of implementation of ‘No Jab, No Pay’. Comparing the average annual vaccination catch-up incidence rate of 6.2% pre-implementation (2012–2015), there was an increase to 9.2% in 2016 (p < .001) and 7.8% in 2017 (p = .027). Secondary outcome measurement of catch-up vaccination incidence rates before (2012–2015) and after (2016–2017) ‘No Jab, No Pay’ implementation showed statistically significant increases for children aged 8–11 years (3.2%–5.6%, p = .038), 12–15 years (7.5%–14.7%, p < .001) and 16–19 years (3.3%–10.2%, p < .001) along with a statistically significant reduction in children aged 1–3 years (11.4%–6.2%, p = .015). Also, catch-up rates for DTPa significantly increased after program implementation. This study demonstrates that the Australian federal government vaccination policy ‘No Jab, No Pay’ was coincident with an increase in catch-up vaccinations within a rural NSW community served by one medical practice, especially for older children.     

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.