Cellulose Acetate Containing Toluidine Blue and Rose Bengal Is an Effective Antimicrobial Coating when Exposed to White Light

Simple methods of reducing the microbial load on surfaces in hospitals are needed to reduce the risk of hospital-associated infections. Here we report on the ability of a cellulose acetate coating containing the photosensitizers toluidine blue and rose bengal to kill microbes (Staphylococcus aureus, Escherichia coli, Clostridium difficile, a bacteriophage, and Candida albicans) on its surface when illuminated with white light

Myc is required for beta-catenin-mediated mammary stem cell amplification and tumorigenesis.

International audienceBACKGROUND: Basal-like breast cancer is a heterogeneous disease characterized by the expression of basal cell markers, no estrogen or progesterone receptor expression and a lack of HER2 overexpression. Recent studies have linked activation of the Wnt/beta-catenin pathway, and its downstream target, Myc, to basal-like breast cancer. Transgenic mice K5DeltaNbetacat previously generated by our team present a constitutive activation of Wnt/beta-catenin signaling in the basal myoepithelial cell layer, resulting in focal mammary hyperplasias that progress to invasive carcinomas. Mammary lesions developed by K5DeltaNbetacat mice consist essentially of basal epithelial cells that, in contrast to mammary myoepithelium, do not express smooth muscle markers. METHODS: Microarray analysis was used to compare K5DeltaNbetacat mouse tumors to human breast tumors, mammary cancer cell lines and the tumors developed in other mouse models. Cre-Lox approach was employed to delete Myc from the mammary basal cell layer of K5DeltaNbetacat mice. Stem cell amplification in K5DeltaNbetacat mouse mammary epithelium was assessed with 3D-culture and transplantation assays. RESULTS: Histological and microarray analyses of the mammary lesions of K5DeltaNbetacat females revealed their high similarity to a subset of basal-like human breast tumors with squamous differentiation. As in human basal-like carcinomas, the Myc pathway appeared to be activated in the mammary lesions of K5DeltaNbetacat mice. We found that a basal cell population with stem/progenitor characteristics was amplified in K5DeltaNbetacat mouse preneoplastic glands. Finally, the deletion of Myc from the mammary basal layer of K5DeltaNbetacat mice not only abolished the regenerative capacity of basal epithelial cells, but, in addition, completely prevented the tumorigenesis. CONCLUSIONS: These results strongly indicate that beta-catenin-induced stem cell amplification and tumorigenesis rely ultimately on the Myc pathway activation and reinforce the hypothesis that basal stem/progenitor cells may be at the origin of a subset of basal-like breast tumors

Inequalities in childhood vaccine uptake: a longitudinal analysis of national coverage in England 2019-23

Objective This study aims to quantify changes in inequalities in childhood vaccination uptake in the context of steadily declining overall childhood vaccination rates in England. Design Cross-sectional longitudinal study. Setting We analysed general practice (GP) level data for five childhood vaccinations (MMR1, MMR2, rotavirus, the pneumococcal (PCV) booster and the six-in-one vaccine) from the Cover of Vaccination Uptake Evaluated Rapidly dataset in England. Participants Children under 5 years of age eligible for paediatric immunisations between April 2019 and March 2023 registered at GPs in England. Main outcome measures Changes in quarterly vaccine uptake over time compared by deprivation level. Regression analyses to quantify the change in inequalities in vaccine uptake over time, expressed as changes in the Slope Index of Inequality (SII). We estimated cumulative susceptibility to measles and rotavirus disease at age five. Results The absolute inequality in vaccine uptake in 2019/20 was largest for MMR2 at 5 years of age (SII -9.8%; 95% CI -9.2 to -10.4). In all vaccinations the SII for uptake increased over the study period: six-in-one -5.1% to -7.8%; rotavirus -7.7% to -10.6%; PCV booster -7.9% to -9.9%; MMR1 at 2 years of age -8.1% to -10.1%, MMR1 -3.3% to -5.9% and MMR2 at 5 years of age -9.8% to -13.7%. The number of measles susceptible children in the least deprived decile increased 15-fold to 20958, and 20-fold to 25345 in the most deprived decile. For rotavirus there was a 14-fold increase in the least deprived decile, and a 16-fold increase in the most deprived decile to 45201. Conclusion Inequalities in childhood vaccination are increasing in England as uptake rates for five key childhood vaccinations have decreased between 2019 and 2023, below the recommended 95% uptake target. Urgent action is needed to strengthen systems for childhood vaccination, with a key focus on reducing inequalities. What is already known on this topic? Uptake rates of childhood vaccinations in England have been steadily declining in the last decade. Socioeconomic deprivation is associated with lower rates of childhood vaccination uptake. What this study adds This analysis of national vaccination coverage data shows decreasing coverage and increasing inequality in five key childhood vaccinations in England from 2019 to 2023. The most pronounced increase in inequality over time is seen in the MMR2 vaccination, with a 40% relative increase, whereby the absolute difference in vaccination uptake rates between GP practices serving the lowest and highest levels of deprivation increased from 9.8% to 13.7% across the study period. Where vaccination catch up is not implemented, an increasing cumulative number of children more susceptible to infection exists as deprivation increases. Policy and practice should respond quickly to address rising socio-economic inequalities in vaccine uptake in children by strengthening systems and tackling the drivers of low vaccination uptake for disadvantaged children

The effectiveness of revaccination with pneumococcal polysaccharide vaccine for preventing pneumococcal disease in older adults in England: A population-based cohort study

Background: Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23). Methods: A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups. Results: Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74–2·20) and IPD (aHR 1·44; 95 %CI 1·41–1·46). In participants aged 64–74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75–2·33) and HP (aHR 1·46; 95 %CI 1·42–1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08–1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94–1·52). Conclusions: No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required