ABSTRACT
Impaired wound healing in the elderly presents a major clinical challenge. Understanding the cellular mechanisms behind age-related impaired healing is vital for developing new wound therapies. Here we show that the actin-remodelling protein, Flightless I (FliI) is a contributing factor to the poor healing observed in elderly skin and that gender plays a major role in this process. Using young and aged, wild-type and FliI overexpressing mice we found that aging significantly elevated FliI expression in the epidermis and wound matrix. Aging exacerbated the negative effect of FliI on wound repair and wounds in aged FliI transgenic mice were larger with delayed reepithelialisation. When the effect of gender was further analysed, despite increased FliI expression in young and aged male and female mice, female FliI transgenic mice had the most severe wound healing phenotype suggesting that male mice were refractory to FliI gene expression. Of potential importance, males, but not females, up-regulated transforming growth factor-beta1 and this was most pronounced in aged male FliI overexpressing wounds. As FliI also functions as a co-activator of the estrogen nuclear receptor, increasing concentrations of beta-estradiol were added to skin fibroblasts and keratinocytes and significantly enhanced FliI expression and translocation of FliI from the cytoplasm to the nucleus was observed. FliI further inhibited estrogen-mediated collagen I secretion suggesting a mechanism via which FliI may directly affect provisional matrix synthesis. In summary, FliI is a contributing factor to impaired healing and strategies aimed at decreasing FliI levels in elderly skin may improve wound repair.
Subject(s)
Aging/physiology , Cytoskeletal Proteins/physiology , Transforming Growth Factor beta1/physiology , Wound Healing/physiology , Animals , Carrier Proteins , Cell Nucleus/metabolism , Cytoplasm/metabolism , Cytoskeletal Proteins/biosynthesis , Estradiol/pharmacology , Female , Fibroblasts/metabolism , Humans , Male , Mice , Mice, Transgenic , Microfilament Proteins , Protein Transport , Sex Factors , Trans-Activators , Up-RegulationABSTRACT
BACKGROUND: Approximately 500 cases of enteric fever, caused by Salmonella enterica serovar Typhi and Paratyphi, are reported in the UK each year. The majority are associated with travel to the Indian subcontinent. The typhoid Vi vaccine protects against S. Typhi and is available to travelers from their general practice or private clinics. The effectiveness of this vaccine has been assessed previously in endemic regions of the world but not in travelers. METHODS: Data from the enhanced surveillance scheme concerning persons in England aged ≥2 years who traveled from the UK and contracted culture-confirmed enteric fever were used to calculate the effectiveness of the vaccine in travelers. A "case-case" case-control design was used, in which patients with typhoid comprised the "cases" and those with paratyphoid acted as "controls." RESULTS: The overall effectiveness of the vaccine, adjusted for age group, sex, ethnicity, birth in a typhoid-endemic country, and year (of receipt of specimen), was 65% (95% confidence interval 53%-73%). Effectiveness did not vary across subgroups of any of the factors in the model, but there was some evidence of waning effectiveness of the vaccine with increasing time since receipt (trend p = 0.05). CONCLUSIONS: The vaccine has been demonstrated to have a similar effectiveness in travelers as that found in endemic populations. It appears to be protective in all ages, including in young children (aged 2-5 years), a finding not consistently replicated in other studies. However, good hygiene practices are necessary in addition to vaccination to prevent infection. The "case-case" case-control design provides a valuable method of calculating the effectiveness of this vaccine in travelers, given the availability of paratyphoid controls, a population with similar demographics and risk exposures.
Subject(s)
Travel , Typhoid Fever/epidemiology , Typhoid-Paratyphoid Vaccines/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Treatment Outcome , Typhoid Fever/microbiology , Typhoid Fever/prevention & control , United Kingdom/epidemiology , Young AdultABSTRACT
Along with recent changes in cannabis legalization and decriminalization, there has been an increasing amount of attention aimed at cannabis use and outcomes in college. Although some amount of cannabis use might be expected under theories of collegiate identity development, public health research indicates that cannabis use ultimately associates with negative vocational outcomes. To examine how cannabis use associates with college grade point average specifically, we surveyed n = 1,080 full-time college students and a replication sample of n = 590. Results showed that even after accounting for other measures of student identity formation and drug use, increased cannabis use was robustly associated with lower grade point average. Future research should examine the mechanisms underlying this association. Nevertheless, while laws and attitudes toward cannabis evolve, initiatives to decrease college use should continue.