Who uses NHS health checks? Investigating the impact of ethnicity and gender and method of invitation on uptake of NHS health checks

Background NHS Health Checks is a national risk assessment prevention programme for all individuals aged 40-74 that reside in England. Through the systematic assessment of an individual’s ten year disease risk, this programme aims to provide early identification and subsequent management of this risk. However, there is limited evidence on how socio-demographic factors impact on uptake and what influence the invitation method has on uptake to this programme. Methods NHS Health Check data from April 2013 to March 2014 was analysed (N = 50,485) for all 30 GP Practices in Luton, a culturally diverse town in England, UK. Data was collected for age, ethnicity, uptake (attendance and non attendance) and invitation method (letter written, verbal face-to-face, telephone). Actual usage of NHS Health Checks was determined for each ethnic group of the population and compared using Chi-square analysis. Results The overall uptake rate for Luton was 44 %, markedly lower that the set target of 50–75 %. The findings revealed a variation of uptake in relation to age, gender, level of deprivation. Ethnicity and gender variations were also found, with ‘White British’ ‘Black Caribbean’ and ‘Indian’ patients most likely to take up a NHS Health Check. However, patients from ‘Any Other White Background’ and ‘Black African’ were significantly less likely to uptake an NHS Health Check compared to all other ethnic groups. Ethnicity and gender differences were also noted in relation to invitation method. Conclusions The findings revealed that different invitation methods were effective for different ethnic and gender groups. Therefore, it is suggested that established protocols of invitation are specifically designed for maximizing the response rate for each population group. Future research should now focus on uncovering the barriers to uptake in particular culturally diverse population groups to determine how public health teams can better engage with these communities

Coupling novel probes with molecular localization microscopy reveals cell wall homeostatic mechanisms in Staphylococcus aureus

Bacterial cell wall peptidoglycan is essential for viability, and its synthesis is targeted by antibiotics, including penicillin. To determine how peptidoglycan homeostasis controls cell architecture, growth, and division, we have developed novel labeling approaches. These are compatible with super-resolution fluorescence microscopy to examine peptidoglycan synthesis, hydrolysis, and the localization of the enzymes required for its biosynthesis (penicillin binding proteins (PBPs)). Synthesis of a cephalosporin-based fluorescent probe revealed a pattern of PBPs at the septum during division, supporting a model of dispersed peptidoglycan synthesis. Metabolic and hydroxylamine-based probes respectively enabled the synthesis of glycan strands and associated reducing termini of the peptidoglycan to be mapped. Foci and arcs of reducing termini appear as a result of both synthesis of glycan strands and glucosaminidase activity of the major peptidoglycan hydrolase, SagB. Our studies provide molecular level details of how essential peptidoglycan dynamics are controlled during growth and division

Development of novel chemical probes to image penicillin binding proteins in Staphylococcus aureus

The shortage of new antibiotics has given rise to unprecedented levels of antimicrobial resistance and demands research into the complex mechanisms utilised by bacteria to adapt, grow and evolve as a species. One of these mechanisms is the dynamicity that bacteria possess to grow and divide whilst maintaining a flexible but rigid structure. The key determinant for these attributes is the unique polymer, peptidoglycan, a major component of eubacterial cell walls responsible for cellular shape and size. Penicillin binding proteins (PBPs) are a group of enzymes that mediate the construction of peptidoglycan and are therefore crucial for cellular viability. They are the target of some of the most clinically effective antibiotics, β-lactams, which operate by inhibiting PBP function, causing cell apoptosis. Despite the function of PBPs being known, certain strains of bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) express PBPs which resist such antibiotics. The reasons behind this are not understood. In addition, the precise roles of PBPs in peptidoglycan assembly and mechanisms which follow their inhibition remain elusive. To help elucidate this, a series of chemical probes were developed to bind to PBPs for imaging in fluorescence microscopy. Novel cephalosporin scaffolds demonstrated good antibacterial activity against Staphylococcus aureus and were subsequently ligated to various fluorescent dyes via click chemistry. Each of the five functionalised chemical probes retained antibacterial activity and successfully imaged PBPs in Staphylococcus aureus using widefield microscopy. The chemical probes displayed specificity for PBPs which was hypothesised to be a result of the size or charge exhibited by each compound. Chemical probe Ceph-1 Cy5 55 imaged PBPs in stochastic optical reconstruction microscopy and gave the highest resolution fluorescent images of PBPs in any organism to date. A potential PBP2a binder was also synthesised for biological testing against MRSA and subsequent ligation to fluorophores. A moenomycin based fluorescent probe to bind to a subset of PBPs and transglycosylase enzymes in Staphylococcus aureus was prepared and demonstrated localised fluorescence in widefield microscopy. A novel oxetanyl dipeptide scaffold was synthesised but did not induce any antibacterial activity. Finally, the chemical methodology for a series oxetanyl phosphonates as potential β-lactamase inhibitors was established

Depletion of HP1α alters the mechanical properties of MCF7 nuclei

Within the nucleus of the eukaryotic cell, DNA is partitioned into domains of highly condensed, transcriptionally silent heterochromatin and less condensed, transcriptionally active euchromatin. Heterochromatin protein 1α (HP1α) is an architectural protein that establishes and maintains heterochromatin, ensuring genome fidelity and nuclear integrity. Although the mechanical effects of changes in the relative amount of euchromatin and heterochromatin brought about by inhibiting chromatin-modifying enzymes have been studied previously, here we measure how the material properties of the nuclei are modified after the knockdown of HP1α. These studies were inspired by the observation that poorly invasive MCF7 breast cancer cells become more invasive after knockdown of HP1α expression and that, indeed, in many solid tumors the loss of HP1α correlates with the onset of tumor cell invasion. Atomic force microscopy (AFM), optical tweezers (OT), and techniques based on micropipette aspiration (MA) were each used to characterize the mechanical properties of nuclei extracted from HP1α knockdown or matched control MCF7 cells. Using AFM or OT to locally indent nuclei, those extracted from MCF7 HP1α knockdown cells were found to have apparent Young’s moduli that were significantly lower than nuclei from MCF7 control cells, consistent with previous studies that assert heterochromatin plays a major role in governing the mechanical response in such experiments. In contrast, results from pipette-based techniques in the spirit of MA, in which the whole nuclei were deformed and aspirated into a conical pipette, showed considerably less variation between HP1α knockdown and control, consistent with previous studies reporting that it is predominantly the lamins in the nuclear envelope that determine the mechanical response to large whole-cell deformations. The differences in chromatin organization observed by various microscopy techniques between the MCF7 control and HP1α knockdown nuclei correlate well with the results of our measured mechanical responses and our hypotheses regarding their origin

Depletion of HP1α alters the mechanical properties of MCF7 nuclei

Within the nucleus of the eukaryotic cell, DNA is partitioned into domains of highly condensed, transcriptionally silent heterochromatin and less condensed, transcriptionally active euchromatin. Heterochromatin protein 1α (HP1α) is an architectural protein that establishes and maintains heterochromatin, ensuring genome fidelity and nuclear integrity. Although the mechanical effects of changes in the relative amount of euchromatin and heterochromatin brought about by inhibiting chromatin-modifying enzymes have been studied previously, here we measure how the material properties of the nuclei are modified after the knockdown of HP1α. These studies were inspired by the observation that poorly invasive MCF7 breast cancer cells become more invasive after knockdown of HP1α expression and that, indeed, in many solid tumors the loss of HP1α correlates with the onset of tumor cell invasion. Atomic force microscopy (AFM), optical tweezers (OT), and techniques based on micropipette aspiration (MA) were each used to characterize the mechanical properties of nuclei extracted from HP1α knockdown or matched control MCF7 cells. Using AFM or OT to locally indent nuclei, those extracted from MCF7 HP1α knockdown cells were found to have apparent Young's moduli that were significantly lower than nuclei from MCF7 control cells, consistent with previous studies that assert heterochromatin plays a major role in governing the mechanical response in such experiments. In contrast, results from pipette-based techniques in the spirit of MA, in which the whole nuclei were deformed and aspirated into a conical pipette, showed considerably less variation between HP1α knockdown and control, consistent with previous studies reporting that it is predominantly the lamins in the nuclear envelope that determine the mechanical response to large whole-cell deformations. The differences in chromatin organization observed by various microscopy techniques between the MCF7 control and HP1α knockdown nuclei correlate well with the results of our measured mechanical responses and our hypotheses regarding their origin