Studying the ssDNA loaded adeno-associated virus aggregation using coarse-grained molecular dynamics simulations.

The aggregation of adeno-associated viral (AAV) capsids in an aqueous environment was investigated via coarse-grained molecular dynamics (CG-MD) simulations. The primary driving force and mechanism of the aggregation were investigated with or without single-strand DNA (ssDNA) loaded at various process temperatures. Capsid aggregation appeared to involve multiple residue interactions (i.e., hydrophobic, polar and charged residues) leading to complex protein aggregation. In addition, two aggregation mechanisms (i.e., the fivefold face-to-face contact and the edge-to-edge contact) were identified from this study. The ssDNA with its asymmetric structure could be the reason for destabilizing protein subunits and enhancing the interaction between the charged residues, and further result in the non-reversible face-to-face contact. At higher temperature, the capsid structure was found to be unstable with the significant size expansion of the loaded ssDNA which could be attributed to reduced number of intramolecular hydrogen bonds, the increased conformational deviations of protein subunits and the higher residue fluctuations. The CG-MD model was further validated with previous experimental and simulation data, including the full capsid size measurement and the capsid internal pressure. Thus, a good understanding of AAV capsid aggregation, instability and the role of ssDNA were revealed by applying the developed computational model.

Pharmaceutical applications of powder-based binder jet 3D printing process - A review.

Pharmaceutical applications of the 3D printing process have recently matured, followed by the FDA approval of Spritam, the first commercial 3D printed dosage form. Due to being a new technology in the conventional dosage formulation field, there is still a dearth of understanding in the 3D printing process regarding the effect of the raw materials on the printed dosage forms and the plausibility of using this technology in dosage development beyond the conventional ways. In this review, the powder-based binder jet 3D printing (BJ3DP) process and its pharmaceutical applications have been discussed, along with a perspective of the formulation development step. The recent applications of BJ3DP in pharmaceutical dosage development, the advantages, and limitations have further been discussed here. A discussion of the critical formulation parameters that need to be explored for the preformulation study of the solid oral dosage development using the BJ3DP process is also presented.

A Successful implementation of an idea to a nationally approved plan: Analyzing Iran's National Health Roadmap using the Kingdon model of policymaking.

Introduction: Hospital beds, human resources, and medical equipment are the costliest elements in the health system and play an essential role at the time of treatment. In this paper, different phases of the NEDA 2026 project and its methodological approach were presented and its formulation process was analysed using the Kingdon model of policymaking. Methods: Iran Health Roadmap (NEDA 2026) project started in March 2016 and ended in March 2017. The main components of this project were hospital beds, clinical human resources, specialist personnel, capital medical equipment, laboratory facilities, emergency services, and service delivery model. Kingdon model of policymaking was used to evaluate NEDA 2026 development and implementation. In this study, all activities to accomplish each step in the Kingdon model was described. Results: The followings were done to accomplish the goals of each step: collecting experts' viewpoint (problem identification and definition), systematic review of the literature, analysis of previous experiences, stakeholder analysis, economic analysis, and feasibility study (solution appropriateness analysis), three-round Delphi survey (policy survey and scrutinization), and intersectoral and interasectoral agreement (policy legislation). Conclusion: In the provision of an efficient health service, various components affect each other and the desired outcome, so they need to be considered as parts of an integrated system in developing a roadmap for the health system. Thus, this study demonstrated the cooperation process at different levels of Iran's health system to formulate a roadmap to provide the necessary resources for the health sector for the next 10 years and to ensure its feasibility using the Kingdon policy framework.

Comparison of the keratometric corneal astigmatism and refractive astigmatism after phacoemulsification and foldable intraocular lens implantation.

Here we aimed to define keratometric and refractive astigmatism in a series of patients who underwent phacoemulsification, using small corneal incision and implantation of foldable intraocular lenses. Furthermore, we compared keratometric astigmatism and refractive astigmatism of the patients both before and after surgery. We performed a follow-up study of patients with newly diagnosed cataract before and after phacoemulsification surgery. Eighty eyes from 78 patients with a mean age of 62.9 ± 12.03 (32-86) years were studied. Thirty-nine (48.8 %) were male and 41(51.2 %) were female. All subjects underwent 3.5 mm corneal incision with the temporal (75 patients; 94 %) or superior (5 patients; 6 %) approach. The patients were followed for a mean of 74.21 ± 71.25 (30-400) days. Patients had higher values of keratometric measurements after surgery compared to those before surgery [45.81 ± 0.11 (45.06-45.94) vs. 45.2 ± 0.20 (44.6-45.41)] (p < 0.001). There was no significant difference in the keratometric astigmatism, refractive astigmatism and keratometry axis pre- and postoperatively. The mean keratometric astigmatism was 0.9 ± 0.54 (0.00-4.00) diopters (D) preoperatively and 0.93 ± 0.45 (0.00-4.00) D postoperatively (p = 0.444). The keratometric axis was 97.7 ± 9.4 preoperatively and 115 ± 15.8 postoperatively (p = 0.185). Refractive astigmatism was 1.15 ± 0.77 (5-180) with the refractive axis of 89.7 ± 5.89 (5-180) degrees in the follow-up (p = 0.752). Ninety percent of the patients had <1.00 D difference in the keratometric and refractive astigmatism, postoperatively. In conclusion while there is no significant difference in postoperative keratometric and refractive astigmatism in most of the eyes, about 10 % show >1 D difference in these measurements.