Predictive Platforms of Bond Cleavage and Drug Release Kinetics for Macromolecule-Drug Conjugates.

Macromolecule-drug conjugates (MDCs) occupy a critical niche in modern pharmaceuticals that deals with the assembly and combination of a macromolecular carrier, a drug cargo, and a linker toward the creation of effective therapeutics. Macromolecular carriers such as synthetic biocompatible polymers and proteins are often exploited for their inherent ability to improve drug circulation, prevent off-target drug cytotoxicity, and widen the therapeutic index of drugs. One of the most significant challenges in MDC design involves tuning their drug release kinetics to achieve high spatiotemporal precision. This level of control requires a thorough qualitative and quantitative understanding of the bond cleavage event. In this review, we highlight specific research findings that emphasize the importance of establishing a precise structure-function relationship for MDCs that can be used to predict their bond cleavage and drug release kinetic parameters.

Evaluation of a dental care program for school beginners in a Paris suburb.

OBJECTIVES: Dental care for children is available in France, but the method of administration is cumbersome: care is generally provided by private dentists, and parents can claim reimbursement of at least 70% of the costs afterwards. In the Département of Val d'Oise (north of Paris and including some densely populated suburbs), a scheme is in place to provide 100% reimbursement. To encourage participation, schoolchildren are screened by dentists who advise if treatment is needed. The objective of this study was to ascertain the effectiveness of screening as a stimulus for seeking dental care. METHODS: In two towns, 6-7-year-old schoolchildren were cluster-sampled to give 507 participants. At screening, about half of the participants were found to be in need of operative treatment. Questionnaires about demographic and other background factors were sent home. From those needing treatment, 186 (77%) sets of questionnaires were returned. These persons were the analytical basis of the study. Six months after screening, the 186 participants were examined to estimate whether they had sought and received treatment as advised. RESULTS: The majority of the participants came from low socioeconomic and deprived backgrounds. Most of the parents were born in countries outside Europe. Only about one-quarter of the children advised to seek treatment had actually done so after 6 months. Slightly under half of those who were treated had claimed the reimbursable amount after the treatment. Of the 186 participants needing treatment, 24% had more than 4 dt + DT but 70% of these had not received any care. CONCLUSION: These findings suggest that even when costs are totally reimbursed, most children in need of care do not receive it; the greater the need of care, the lower the likelihood of getting it. The deprived people and immigrants frequently inhabiting the Parisian suburbs seem to experience cultural, financial, linguistic, and administrative barriers to care, which impede uptake and which must be changed if these children are to enjoy improved dental health.

Dynamical effects in strain measurements by dark-field electron holography.

Here, we study the effect of dynamic scattering on the projected geometric phase and strain maps reconstructed using dark-field electron holography (DFEH) for non-uniformly strained crystals. The investigated structure consists of a {SiGe/Si} superlattice grown on a (001)-Si substrate. The three-dimensional strain field within the thin TEM lamella is modelled by the finite element method. The observed projected strain is simulated in two ways by multiplying the strain at each depth in the crystal by a weighting function determined from a recently developed analytical two-beam dynamical theory, and by simply taking the average value. We demonstrate that the experimental results need to be understood in terms of the dynamical theory and good agreement is found between the experimental and simulated results. Discrepancies do remain for certain cases and are likely to be from an imprecision in the actual two-beam diffraction conditions, notably the deviation parameter, and points to limitations in the 2-beam approximation. Finally, a route towards a 3D reconstruction of strain fields is proposed.