Platinum(II)-based DNA intercalators where the intercalating ligand is 1,10-phenanthroline or a phenanthroline derivative and where the ancillary ligand is either achiral (e.g. ethylenediamine) or chiral (e.g. diaminocyclohexane) show a range of cytotoxicities with a defined structure–activity relationship. The most cytotoxic are those that contain methylated-phenanthroline ligands and 1S,2S-diaminocyclohexane (S,S-dach) as the ancillary ligand. We have developed a new purification method using Sep-Pak® C-18 reverse phase columns, which means these metal complexes can be made faster and cheaper compared to published methods. Platinum(II)-based complexes containing imidazole, pyrrole and β-alanine subunits, that are capable of recognising specific DNA base-pair sequences have also been synthesised. These include linear or hairpin polyamide ligands that can recognise DNA sequences up to seven base-pairs in length and contain single platinum centres capable of forming monofunctional adducts with DNA. We have now synthesised and characterised, by ¹H and ¹⁹⁵Pt NMR, ESI-MS and elemental analysis, the first dinuclear platinum(II) DNA sequence selective agent. Finally, using ¹H NMR we have examined the encapsulation of our platinum(II)-based DNA intercalators by cucurbit[6]uril (CB[6]). Encapsulation by CB[6] was found to not significantly change the cytotoxicity of five platinum(II)-based DNA intercalators, indicating it may have utility as a molecular carrier for improved drug delivery.

Objectives In considering explanations for poor maternal and newborn health outcomes, many investigations have focused on the decision-making patterns and actions of expectant mothers and families, as opposed to exploring the ‘supply side’ (health service provider) barriers. Thus, we examined the health system factors impacting on access to and delivery of quality maternal and newborn healthcare in rural settings. Design A semistructured qualitative study using face-to-face in-depth interviews with health professionals, and focus group sessions with community members, in eight project sites in two districts of Upper West Region, Ghana, was employed. Participants were purposively selected to generate relevant data to help address the study objective. The survey was guided by WHO standard procedures and Ghana Health Ministry’s operational work plan for maternal and newborn care. Setting Nadowli–Kaleo and Daffiama–Bussie–Issa districts in Upper West Region, Ghana. Participants Two hundred and fifty-three participants were engaged in the study through convenient and purposive sampling: healthcare professionals (pharmacist, medical doctor, two district directors of health services, midwives, community health and enrolled nurses) (n=13) and community members comprising opinion leaders, youth leaders and adult non-pregnant women (n=240 in 24 units of focus groups). Results Results show significant barriers affecting the quality and appropriateness of maternal and neonatal health services in the rural communities and the Nadowli District Hospital. The obstacles were inadequate medical equipment and essential medicines, infrastructural challenges, shortage of skilled staff, high informal costs of essential medicines and general limited capacities to provide care. Conclusion Implementation of the birth preparedness and complication readiness strategy is in its infancy at the health facility level in the study areas. Increasing the resources at the health provider level is essential to achieving international targets for maternal and neonatal health outcomes and for bridging inequities in access to essential maternal and newborn healthcare.

It is widely accepted that all medical graduates should understand the uses and methods of rigorous research, with a need to promote research to graduates who will pursue an academic career. This study aimed to explore, identify and explain what motivates and demotivates medical students to do research. A convergent parallel mixed methods study was conducted. Cross-sectional quantitative survey data (n = 579) and qualitative semi-structured interview findings (n = 23) data were separately collected and analysed. Informed by Self-Determination Theory (SDT), quantitative and qualitative findings were integrated to develop a model for the factors associated with medical students’ expressed motivation to do research, and related to clinical and research learning activities at different stages in an undergraduate medical program. Only 7.5 % of students had research experience prior to entering the program. Survey results revealed that students who had experienced exposure to the uncertainties of clinical practice through clerkships (Pre-Clinical (48 %) vs Clinical Years (64 %), p < 0.001), and a sense of achievement through supported compulsory research activities which were conducted as a team (Pre- Community Research (51 %) vs Post-Community Research (66 %), p < 0.001), were more likely to view future research activities positively. When integrated with qualitative findings using the three SDT domains of autonomy, competence and relatedness, eight major themes were identified: Self & Time, Career, Bureaucracy, Financial, Confidence, Clinical Relevance, Research as a Social Activity, and Personal Relevance. The findings suggest that motivation to do research is associated with increasing internalization of intrinsic motivators; in particular those associated with competence (Confidence) and relatedness (Clinical Relevance, Research as a Social Activity). SDT is useful for understanding the motivation of individuals and how curriculum can be designed to optimise motivation. Study findings suggest that well supported compulsory research activities that incorporate group learning and elements of choice may promote motivation to do research, and potentially, careers in research, even in a research naive student body.

The co-infection of porcine reproductive respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) is quite common in clinical settings and no effective treatment to the co-infection is available. In this study, we established the porcine alveolar macrophages (PAM) cells model co-infected with PRRSV/PCV2 with modification in vitro, and investigated the antiviral activity of Matrine on this cell model and further evaluated the effect of Matrine on virus-induced TLR3,4/NF-κB/TNF-α pathway. The results demonstrated PAM cells inoculated with PRRSV followed by PCV2 2 h later enhanced PRRSV and PCV2 replications. Matrine treatment suppressed both PRRSV and PCV2 infection at 12 h post infection. Furthermore, PRRSV/PCV2 co- infection induced IκBα degradation and phosphorylation as well as the translocation of NF-κB from the cytoplasm to the nucleus indicating that PRRSV/PCV2 co-infection induced NF-κB activation. Matrine treatment significantly down-regulated the expression of TLR3, TLR4 and TNF-α although it, to some extent, suppressed p-IκBα expression, suggesting that TLR3,4/NF-κB/TNF-α pathway play an important role of Matrine in combating PRRSV/PCV2 co-infection. It is concluded that Matrine possesses activity against PRRSV/PCV2 co-infection in vitro and suppression of the TLR3,4/NF-κB/TNF-α pathway as an important underlying molecular mechanism. These findings warrant Matrine to be further explored for its antiviral activity in clinical settings.