Adapting a nurse-led primary care initiative to cardiovascular disease control in Ghana: a qualitative study.

BACKGROUND: Cardiovascular Disease (CVD) is a growing cause of morbidity and mortality in Ghana, where rural primary health care is provided mainly by the Community-based Health Planning and Services (CHPS) initiative. CHPS locates nurses in community-level clinics for basic curative and preventive health services and provides home and outreach services. But CHPS currently lacks capacity to screen for or treat CVD and its risk factors. METHODS: In two rural districts, we conducted in-depth interviews with 21 nurses and 10 nurse supervisors to identify factors constraining or facilitating CVD screening and treatment. Audio recordings were transcribed, coded for content, and analyzed for key themes. RESULTS: Respondents emphasized three themes: community demand for CVD care; community access to CVD care; and provider capacity to render CVD care. Nurses and supervisors noted that community members were often unaware of CVD, despite high reported prevalence of risk factors. Community members were unable to travel for care or afford treatment once diagnosed. Nurses lacked relevant training and medications for treating conditions such as hypertension. Respondents recognized the importance of CVD care, expressed interest in acquiring further training, and emphasized the need to improve ancillary support for primary care operations. CONCLUSIONS: CHPS staff expressed multiple constraints to CVD care, but also cited actions to address them: CVD-focused training, provision of essential equipment and pharmaceuticals, community education campaigns, and referral and outreach transportation equipment. Results attest to the need for trial of these interventions to assess their impact on CVD risk factors such as hypertension, depression, and alcohol abuse.

Exploring the Effects of Chirality of 5-methyl-5-[4-(4-oxo-3H-quinazolin-2-yl) phenyl]imidazolidine-2,4-dione and its Derivatives on the Oncological Target Tankyrase 2. Atomistic Insights.

BACKGROUND: Tankyrases (TNKS) are homomultimers existing in two forms, viz. TNKS1 and TNKS2. TNKS2 plays a pivotal role in carcinogenesis by activating the Wnt//ß-catenin pathway. TNKS2 has been identified as a suitable target in oncology due to its crucial role in mediating tumour progression. The discovery of 5-methyl-5-[4-(4-oxo-3H-quinazolin-2-yl) phenyl] imidazolidine-2,4-dione, a hydantoin phenylquinazolinone derivative which exists as a racemic mixture and in its pure enantiomer forms, has reportedly exhibited inhibitory potency towards TNKS2. However, the molecular events surrounding its chirality towards TNKS2 remain unresolved. METHODS: Herein, we employed in silico methods such as molecular dynamics simulation coupled with binding free energy estimations to explore the mechanistic activity of the racemic inhibitor and its enantiomer forms on TNK2 at a molecular level Results: Favourable binding free energies were noted for all three ligands propelled by electrostatic and van der Waals forces. The positive enantiomer demonstrated the highest total binding free energy (-38.15 kcal/mol), exhibiting a more potent binding affinity to TNKS2. Amino acids PHE1035, ALA1038, and HIS1048; PHE1035, HIS1048 and ILE1039; and TYR1060, SER1033 and ILE1059 were identified as key drivers of TNKS2 inhibition for all three inhibitors, characterized by the contribution of highest residual energies and the formation of crucial high-affinity interactions with the bound inhibitors. Further assessment of chirality by the inhibitors revealed a stabilizing effect of the complex systems of all three inhibitors on the TNKS2 structure. Concerning flexibility and mobility, the racemic inhibitor and negative enantiomer revealed a more rigid structure when bound to TNKS2, which could potentiate biological activity interference. The positive enantiomer, however, displayed much more elasticity and flexibility when bound to TNKS2. CONCLUSION: Overall, 5-methyl-5-[4-(4-oxo-3H-quinazolin-2-yl) phenyl] imidazolidine-2,4-dione and its derivatives showed their inhibitory prowess when bound to the TNKS2 target via in silico assessment. Thus, results from this study offer insight into chirality and the possibility of adjustments of the enantiomer ratio to promote greater inhibitory results. These results could also offer insight into lead optimization to enhance inhibitory effects.