Targeting intracellular, multi-drug resistant Staphylococcus aureus with guanidinium polymers by elucidating the structure-activity relationship

Intracellular persistence of bacteria represents a clinical challenge as bacteria can thrive in an environment protected from antibiotics and immune responses. Novel targeting strategies are critical in tackling antibiotic resistant infections. Synthetic antimicrobial peptides (SAMPs) are interesting candidates as they exhibit a very high antimicrobial activity. We first compared the activity of a library of ammonium and guanidinium polymers with different sequences (statistical, tetrablock and diblock) synthesized by RAFT polymerization against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive strains (MSSA). As the guanidinium SAMPs were the most potent, they were used to treat intracellular S. aureus in keratinocytes. The diblock structure was the most active, reducing the amount of intracellular MSSA and MRSA by two-fold. We present here a potential treatment for intracellular, multi-drug resistant bacteria, using a simple and scalable strategy

Looped flow RAFT polymerization for multiblock copolymer synthesis

A looped flow process was designed for the synthesis of well-defined multiblock copolymers using reversible addition–fragmentation chain transfer (RAFT) polymerization. The reaction conditions were optimized to reach high conversions whilst maintaining a high end-group fidelity. The loop set-up proved to be a flexible, robust and time-efficient process for scaling-up multiblock copolymers

Blood pressure self-monitoring in pregnancy (BuMP) feasibility study; a qualitative analysis of women's experiences of self-monitoring

Background Hypertensive disorders in pregnancy are a leading cause of maternal and fetal morbidity worldwide. Raised blood pressure (BP) affects 10% of pregnancies worldwide, of which almost half develop pre-eclampsia. The proportion of pregnant women who have risk factors for pre-eclampsia (such as pre-existing hypertension, obesity and advanced maternal age) is increasing. Pre-eclampsia can manifest itself before women experience symptoms and can develop between antenatal visits. Incentives to improve early detection of gestational hypertensive disorders are therefore strong and self-monitoring of blood pressure (SMBP) in pregnancy might be one means to achieve this, whilst improving women’s involvement in antenatal care. The Blood Pressure Self-Monitoring in Pregnancy (BuMP) study aimed to evaluate the feasibility and acceptability of SMBP in pregnancy. Methods To understand women’s experiences of SMBP during pregnancy, we undertook a qualitative study embedded within the BuMP observational feasibility study. Women who were at higher risk of developing hypertension and/or pre-eclampsia were invited to take part in a study using SMBP and also invited to take part in an interview. Semi-structured interviews were conducted at the women’s homes in Oxfordshire and Birmingham with women who were self-monitoring their BP as part of the BuMP feasibility study in 2014. Interviews were conducted by a qualitative researcher and transcribed verbatim. A framework approach was used for analysis. Results Fifteen women agreed to be interviewed. Respondents reported general willingness to engage with monitoring their own BP, feeling that it could reduce anxiety around their health during pregnancy, particularly if they had previous experience of raised BP or pre-eclampsia. They felt able to incorporate self-monitoring into their weekly routines, although this was harder post-partum. Self-monitoring of BP made them more aware of the risks of hypertension and pre-eclampsia in pregnancy. Feelings of reassurance and empowerment were commonly reported by the women in our sample

Gathering opinion leader data for a tailored implementation intervention in secondary healthcare: a randomised trial

Background: Health professionals’ behaviour is a key component in compliance with evidence-based recommendations. Opinion leaders are an oft-used method of influencing such behaviours in implementation studies, but reliably and cost effectively identifying them is not straightforward. Survey and questionnaire based data collection methods have potential and carefully chosen items can – in theory – both aid identification of opinion leaders and help in the design of an implementation strategy itself. This study compares two methods of identifying opinion leaders for behaviour-change interventions. Methods: Healthcare professionals working in a single UK mental health NHS Foundation Trust were randomly allocated to one of two questionnaires. The first, slightly longer questionnaire, asked for multiple nominations of opinion leaders, with specific information about the nature of the relationship with each nominee. The second, shorter version, asked simply for a list of named “champions” but no more additional information. We compared, using Chi Square statistics, both the questionnaire response rates and the number of health professionals likely to be influenced by the opinion leaders (i.e. the “coverage” rates) for both questionnaire conditions. Results: Both questionnaire versions had low response rates: only 15% of health professionals named colleagues in the longer questionnaire and 13% in the shorter version. The opinion leaders identified by both methods had a low number of contacts (range of coverage, 2–6 each). There were no significant differences in response rates or coverage between the two identification methods. Conclusions: The low response and population coverage rates for both questionnaire versions suggest that alternative methods of identifying opinion leaders for implementation studies may be more effective. Future research should seek to identify and evaluate alternative, non-questionnaire based, methods of identifying opinion leaders in order to maximise their potential in organisational behaviour change interventions

Blood pressure self-monitoring in pregnancy: examining feasibility in a prospective cohort study

Background: Raised blood pressure (BP) affects approximately 10% of pregnancies worldwide, and a high proportion of affected women develop pre-eclampsia. This study aimed to evaluate the feasibility of self-monitoring of BP in pregnancy in women at higher risk of pre-eclampsia. Methods: This prospective cohort study of self-monitoring BP in pregnancy was carried out in two hospital trusts in Birmingham and Oxford and thirteen primary care practices in Oxfordshire. Eligible women were those defined by the UK National Institute for Health and Care Excellence (NICE) guidelines as at higher risk of pre-eclampsia. A total of 201 participants were recruited between 12 and 16 weeks of pregnancy and were asked to take two BP readings twice daily three times a week through their pregnancy. Primary outcomes were recruitment, retention and persistence of self-monitoring. Study recruitment and retention were analysed with descriptive statistics. Survival analysis was used to evaluate the persistence of self-monitoring and the performance of self-monitoring in the early detection of gestational hypertension, compared to clinic BP monitoring. Secondary outcomes were the mean clinic and self-monitored BP readings and the performance of self-monitoring in the detection of gestational hypertension and pre-eclampsia compared to clinic BP. Results: Of 201 women recruited, 161 (80%) remained in the study at 36 weeks or to the end of their pregnancy, 162 (81%) provided any home readings suitable for analysis, 148 (74%) continued to self-monitor at 20 weeks and 107 (66%) at 36 weeks. Self-monitored readings were similar in value to contemporaneous matched clinic readings for both systolic and diastolic BP. Of the 23 who developed gestational hypertension or pre-eclampsia and self-monitored, 9(39%) had a raised home BP prior to a raised clinic BP. Conclusions: Self-monitoring of BP in pregnancy is feasible and has potential to be useful in the early detection of gestational hypertensive disorders but maintaining self-monitoring throughout pregnancy requires support and probably enhanced training

Oligomeric Cationic Polymethacrylates: A Comparison of Methods for Determining Molecular Weight

This study compares three common laboratory methods, size-exclusion chromatography (SEC), ¹H nuclear magnetic resonance (NMR), and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), to determine the molecular weight of oligomeric cationic copolymers. The potential bias for each method was examined across a series of polymers that varied in molecular weight and cationic character (both choice of cation (amine versus guanidine) and relative proportion present). SEC was found to be the least accurate, overestimating <i>M</i>_n by an average of 140%, owing to the lack of appropriate cationic standards available, and the complexity involved in estimating the hydrodynamic volume of copolymers. MALDI-TOF approximated <i>M</i>_n well for the highly monodisperse (<i>Đ</i> < 1.1), low molecular weight (degree of polymerization (DP) <50) species but appeared unsuitable for the largest polymers in the series due to the mass bias associated with the technique. ¹H NMR was found to most accurately estimate <i>M</i>_n in this study, differing to theoretical values by only 5.2%. ¹H NMR end-group analysis is therefore an inexpensive and facile, primary quantitative method to estimate the molecular weight of oliogomeric cationic polymethacrylates if suitably distinct end-groups signals are present in the spectrum