1. Refinement of Computational Access to Molecular Physicochemical Properties: From Ro5 to bRo5
Matteo Rossi Sebastiano, Diego Garcia Jimenez, Maura Vallaro, Giulia Caron, Giuseppe Ermondi J Med Chem. 2022 Sep 22;65(18):12068-12083.doi: 10.1021/acs.jmedchem.2c00774.Epub 2022 Sep 12.
There is a need of computational tools to rank bRo5 drug candidates in the very early phases of drug discovery when chemical matter is unavailable. In this study, we selected three compounds: (a) a Ro5 drug (Pomalidomide), (b) a bRo5 orally available drug (Saquinavir), and (c) a polar PROTAC (CMP 98) to focus on computational access to physicochemical properties. To provide a benchmark, the three compounds were first experimentally characterized for their lipophilicity, polarity, IMHBs, and chameleonicity. To reproduce the experimental information content, we generated conformer ensembles with conformational sampling and molecular dynamics in both water and nonpolar solvents. Then we calculated Rgyr, 3D PSA, and IMHB number. An innovative pool of strategies for data analysis was then provided. Overall, we report a contribution to close the gap between experimental and computational methods for characterizing bRo5 physicochemical properties.
2. Does Calcium Hydroxide Reduce Endotoxins in Infected Root Canals? Systematic Review and Meta-analysis
Natália Rocha Bedran, Patricia Nadelman, Marcela Baraúna Magno, Aline de Almeida Neves, Daniele Masterson Ferreira, Andréa Vaz Braga Pintor, Lucianne Cople Maia, Laura Guimarães Primo J Endod. 2020 Nov;46(11):1545-1558.doi: 10.1016/j.joen.2020.08.002.Epub 2020 Aug 11.
Introduction:The purpose of this study was to evaluate the potential of endotoxin reduction by comparing the number of lipopolysaccharides (LPSs) before and after the use of calcium hydroxide (Ca[OH]2) as intracanal medication (ICM). Methods:Searches were performed up to June 2020. Clinical and experimental studies comparing the amount of LPSs before and after the use of Ca(OH)2 as ICM in infected root canals were included. Risks of bias assessment and data extraction were performed. Meta-analysis was conducted by subgrouping according to Ca(OH)2, the presence of an antimicrobial substance (AS), irrigant solution during chemomechanical preparation (CMP), and the incidence of LPS reduction. The certainty of evidence was determined by the Grading of Recommendations Assessment, Development and Evaluation approach. Results:Nine studies were included in the qualitative synthesis and 7 in the meta-analysis. Three articles had low risk of bias (RB), 1 had moderate RB, 2 had high RB, and 3 "some concerns." Overall, Ca(OH)2, with or without AS, reduced mean LPSs before CMP (standardized mean difference [SMD] = -1.087 [confidence interval {CI}, -1.453 to -0.721], P < .001, I2 = 58.7%) and after CMP (SMD = -0.919 [CI, -1.156 to -0.682], P < .001, I2 = 24.7%). Considering the irrigant solutions, the overall results showed a reduction before (SMD = -1.053 [CI, -1.311 to -0.795], P < .001, I2 = 58.7%) and after CMP (SMD = -0.938 [CI, -1.147 to -0.729], P < .001, I2 = 24,6%). Analyses presented very low certainty of evidence. The incidence of LPS reduction was 98.9% and 61.7% for Ca(OH)2 with and without AS, respectively.Conclusions:Ca(OH)2 reduces endotoxin levels when used as ICM but is unable to eliminate LPSs completely independent of the irrigating solution used with very low certainty of evidence.
3. Child Maltreatment Prevention Readiness Assessment in Oman
Muna Al Saadoon, Asia Al Numani, Hassan Saleheen, Maha Almuneef, Majid Al-Eissa Sultan Qaboos Univ Med J. 2020 Feb;20(1):e37-e44.doi: 10.18295/squmj.2020.20.01.006.Epub 2020 Mar 9.
Objectives:This study aimed to evaluate Oman's readiness for implementing large-scale child maltreatment prevention (CMP) programmes. Methods:This cross-sectional study was conducted between May and August 2016 in Oman. Participants, referred to as key informants, were individuals with influence and decision-making powers over CMP. The multidimensional Readiness Assessment for the Prevention of Child Maltreatment tool, developed by the World Health Organization with the help of collaborators from middle- and low-income countries, was used to assess 10 dimensions of readiness, each with a maximum score of 10. Results:A total of 49 participants were included in this study (response rate = 98%). The mean total score for the 10 dimensions was 50.17 out of 100 possible points. The participants showed high mean readiness scores on legislation, mandates and policies (9.08) followed by knowledge of CMP (7.55), institutional resources and links (6.12), willingness to address the problem (5.35), informal social resources (5.15) and current programme implementation and evaluation (5.10). Participants had low scores in readiness in association with human and technical resources (2.44), attitudes towards CMP (2.90), scientific data on CMP (3.06) and material resources (3.46).Conclusion:The results of this study indicate that Oman has a moderate level of readiness to implement large-scale evidence-based prevention programmes against child maltreatment; however, several dimensions still need to be strengthened. It is important to develop a national strategy that outlines a framework for organising and prioritising efforts towards CMP.
