COVID-19 Public Health Measures and Patient and Public Involvement in Health and Social Care Research: An Umbrella Review.

An umbrella review of previously published systematic reviews was conducted to determine the nature and extent of the patient and public involvement (PPI) in COVID-19 health and social care research and identify how PPI has been used to develop public health measures (PHM). In recent years, there has been a growing emphasis on PPI in research as it offers alternative perspectives and insight into the needs of healthcare users to improve the quality and relevance of research. In January 2022, nine databases were searched from 2020-2022, and records were filtered to identify peer-reviewed articles published in English. From a total of 1437 unique records, 54 full-text articles were initially evaluated, and six articles met the inclusion criteria. The included studies suggest that PHM should be attuned to communities within a sociocultural context. Based on the evidence included, it is evident that PPI in COVID-19-related research is varied. The existing evidence includes written feedback, conversations with stakeholders, and working groups/task forces. An inconsistent evidence base exists in the application and use of PPI in PHM. Successful mitigation efforts must be community specific while making PPI an integral component of shared decision-making.

Kaempferol as a Potential PAK4 Inhibitor in Triple Negative Breast Cancer: Extra Precision Glide Docking and Free Energy Calculation.

BACKGROUND: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many human tumors, particularly in Triple Negative Breast Cancer (TNBC) progression. Studies have revealed the crucial role of PAK4 in cell proliferation, anchorage-independent growth and cell migration among other hallmarks of cancer. Thus, PAK4 is an attractive target for anti-TNBC drug design and development. In our research, we used in silico methods to investigate the inhibitory potentials of kaempferol against PAK4 as compared with co-crystallized 4T6 and a standard PAK4 inhibitor-KPT-9274. The ligands were docked into the ATP-binding site of the target enzyme and post-docking validations were calculated. RESULTS: In the molecular docking results, kaempferol had higher affinity than the standard KPT-9274. However, the SP and XP docking scores for the co-crystallized 4T6 were the highest. The analyses of the docking showed a favorable interaction between kaempferol and the catalytic-important aminoacyl residues, especially GLU396, LEU398 and ASP458 in the ATP-binding site of PAK4 when compared with what was obtained in the 4T6-PAK4 complex. Molecular mechanics based MM-GBSA was used to validate docking results. The free energy calculations revealed that kaempferol may have a favorable biological activity. Furthermore, the druggability of each ligand was assessed using the QikProp module and the SwissADME online tool. Kaempferol possessed a propitious drug-like property when compared to the standard ligands. CONCLUSIONS: We, therefore, put forward a logical argument that kaempferol can be further evaluated as a potential PAK4 inhibitor in TNBC.