Co-culturing experiments reveal the uptake of myo-inositol phosphate synthase (EC 5.5.1.4) in an inositol auxotroph of Saccharomyces cerevisiae.

BACKGROUND: Myo-Inositol Phosphate Synthase (MIP) catalyzes the conversion of glucose 6- phosphate into inositol phosphate, an essential nutrient and cell signaling molecule. Data obtained, first in bovine brain and later in plants, established MIP expression in organelles and in extracellular environments. A physiological role for secreted MIP has remained elusive since its first detection in intercellular space. To provide further insight into the role of MIP in intercellular milieus, we tested the hypothesis that MIP may function as a growth factor, synthesizing inositol phosphate in intercellular locations requiring, but lacking ability to produce or transport adequate quantities of the cell-cell communicator. This idea was experimentally challenged, utilizing a Saccharomyces cerevisiae inositol auxotroph with no MIP enzyme, permeable membranes with a 0.4 µm pore size, and cellular supernatants as external sources of inositol isolated from S. cerevisiae cells containing either wild-type enzyme (Wt-MIP), no MIP enzyme, auxotroph (Aux), or a green fluorescent protein (GFP) tagged reporter enzyme (MIP- GFP) in co- culturing experiments. RESULTS: Resulting cell densities and microscopic studies with corroborating biochemical and molecular analyses, documented sustained growth of Aux cells in cellular supernatant, concomitant with the uptakeof MIP, detected as MIP-GFP reporter enzyme. These findings revealed previously unknown functions, suggesting that the enzyme can: (1) move into and out of intercellular space, (2) traverse cell walls, and (3) act as a growth factor to promote cellular proliferation of an inositol requiring cell. CONCLUSIONS: Co-culturing experiments, designed to test a probable function for MIP secreted in extracellular vesicles, uncovered previously unknown functions for the enzyme and advanced current knowledge concerning spatial control of inositol phosphate biosynthesis. Most importantly, resulting data identified an extracellular vesicle (a non-viral vector) that is capable of synthesizing and transporting inositol phosphate, a biological activity that can be used to enhance specificity of current inositol phosphate therapeutics.

Enrolling a rural community pharmacy as a Vaccines for Children provider to increase HPV vaccination: a feasibility study.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the U.S. with over 80 million infected individuals. High-risk strains are associated with 6 different cancers. Although infection is preventable, U.S. vaccination rates remain suboptimal and there are noted disparities between urban and rural communities due to economic barriers, lack of access, and low awareness and education. METHODS: The current pilot study sought to overcome these barriers through an interprofessional collaborative enrolling a community pharmacy in a rural, medically underserved Alabama county as a Vaccines for Children (VFC) provider to provide free vaccines to eligible adolescents. Program evaluation was conducted to determine the intervention's feasibility. Potential efficacy was assessed by analyzing county-level HPV vaccination uptake and completion rates using state immunization registry data. RESULTS: Over the 8-month study, 166 total vaccines were administered to 89 adolescents ages 10-18, including 55 doses of HPV vaccine, 53 doses of Tdap vaccine, 45 doses of meningococcal vaccine, and 13 doses of influenza vaccine. Among these adolescents, mean age was 12.6 years old, and 64 (71.9%) were VFC patients. The pharmacy recorded an increase in total vaccine administration of 158.8%, an increase in prescription revenue of 34.8%, and an increase in total revenue by 24.4% during the course of the study, compared to the previous year. CONCLUSIONS: Findings from the current work demonstrate the potential of this strategy and can serve as a blueprint for statewide and national dissemination and implementation to ultimately increase access to vaccination services, increase vaccination rates, and reduce urban-rural vaccine disparities.

Factors Associated with HPV Vaccination Uptake and HPV-Associated Cancers: A County-Level Analysis in the State of Alabama.

Despite availability of a safe, effective vaccination, uptake and completion rates of human papillomavirus (HPV) vaccination remain low in the United States. This is particularly true in the southeast, which also sees some of the highest rates of HPV-associated (HPVa) cancers. We aimed to identify areas in Alabama in need of intervention with respect to HPVa cancers and HPV vaccination, and factors potentially associated with these rates by performing county-level secondary data analysis using state and national data sources. Alabama ranks 15th nationally in HPVa cancer rates, with 66.7% and 80.8% of counties having higher HPVa cancer rates than the national incidences of males and females, respectively. Regarding HPV vaccination, 95.5% and 98.5% of Alabama's counties have uptake rates less than the national averages for males and females, respectively. The seven counties with the highest HPV vaccination uptake ranged in rates from 60.2 to 73.6%. Counties with the highest HPV vaccination rates for adolescents were majority African American with low adult educational attainment rates and high rates of poverty and publicly-insured children/adolescents. These counties were also located in Alabama's Black Belt region, traditionally known for low socioeconomics, reduced access to social services, and negative health outcomes. Some counties with the highest rates of HPVa cancers also had among the highest rates of HPV vaccination, indicating a potential association between perceived susceptibility and desire to get HPV vaccine in these communities, warranting further investigation. Future work is needed to translate these findings into actionable intervention practices to increase HPV vaccination.