Healthcare Technologies and Methods (United States)

Background:While pharmacists have provided vaccinations to patients in the communitypharmacy setting, pharmacist involvement within the medical office settingis not well documented in the literature. The American Society ofHealth-System Pharmacists reports that ambulatory care pharmacists arescreening for and administering vaccinations at a declining rate, despitestandards of practice. Vaccination rates for adults 19–64 years of ageremain low, based on Healthy People 2020 goals, putting them at risk forvaccine-preventable diseases.Objectives:The aim of the study was to assess vaccination rates of ambulatory carepharmacy clinic patients aged 19–64 years and to compare the rates betweenthree clinics and to Healthy People 2020 goals.Methods:This was a baseline retrospective analysis of vaccination rates for patientsaged 19–64 years who attended at least one pharmacy clinic visit at one ofthe three medical office practices. Age, sex, medical conditions, cigaretteor alcohol use, immunosuppressive medications, and vaccines recommended andreceived were recorded. Vaccination status was assessed according to theAdvisory Committee for Immunization Practices recommendations. Data werecollected from January 2016 to March 2017. The percentage of eligiblepatients who received each vaccine was determined overall and for eachclinic.Results:There were 240 patients who met the inclusion criteria, with a mean age of52.8 years. The percentage of patients with vaccination documented in themedical record was 25% for pneumococcal conjugate, 35.7% for pneumococcalpolysaccharide, 26.9% for zoster vaccine live, 6.4% for hepatitis B, and50.6% for tetanus toxoid, reduced diphtheria toxoid, and acellularpertussis. Vaccination rates for pneumococcal conjugate, pneumococcalpolysaccharide, and zoster vaccine live were below established HealthyPeople 2020 goals.Conclusion:Vaccination rates remain low in adults 19–64 years of age. Ambulatory carepharmacists should consider assessing vaccination status during clinicvisits as a component of comprehensive vaccination programs.

Crucial cellular decisions that lead to cell growth, metabolism, proliferation, and survival are all dependent on the precise control of the phosphorylation state of proteins. The serine/threonine phosphatase, PHLPP (PH domain leucine-rich repeat protein phosphatase) has been shown to directly dephosphorylate several members of the AGC family of kinases. Knockdown of PHLPP1 by siRNA in neonatal cardiomyocytes potentiates Akt activity and phosphorylation specifically at Ser473 basally and following agonist stimulation while, the removal of PHLPP2 in cardiomyocytes does not affect Akt phosphorylation as previously reported in other cells. We hypothesize that PHLPP2 may target other AGC kinases in cardiomyocytes to regulate cardiac hypertrophy. Preliminary data suggests that removal of PHLPP2 activates fetal gene re-expression at baseline and potentiates phenylephrine (PE) induced gene expression 2 fold over siControl. Recently, G protein-coupled receptor kinase 5 (GRK5), which is an AGC kinase, has been shown to regulate cardiac hypertrophy through HDAC5 phosphorylation and de-repression of gene transcription. We wanted to determine whether PHLPP2 regulates GRK5 phosphorylation and localization in cardiomyocytes. GRK5 translocates to the nucleus following hypertrophic stimulation and we found that removal of PHLPP2 increased GRK5 translocation to the nucleus at baseline and with PE treatment compared to siControl cells. Also, removal of PHLPP2 increased nuclear export of HDAC5 at baseline and following PE treatment. Conversely, overexpression of PHLPP2 blocked nuclear translocation of GRK5 following PE treatment. Ongoing studies will determine whether PHLPP acts as a scaffold or if its phosphatase activity is necessary for inhibition of GRK5 translocation by directly measuring the phosphorylation of GRK5 in the presence and absence of PHLPP2 following hypertrophic stimulation. Our preliminary data is the first to uncover GRK5 as a novel PHLPP2 target in cardiomyocytes. Since little is known about the non-canonical regulation of GRK5, understanding whether phosphorylation and localization is regulated within the cardiomyocyte by PHLPP has potential for new therapeutic targets in the treatment of cardiac hypertrophy and failure.

The serine/threonine kinase Akt, also known as protein kinase B (PKB), regulates a wide variety of cellular processes including metabolism, cell growth, survival, protein synthesis, and gene transcription. Akt is activated by upstream kinases through sequential phosphorylation on its activation loop (Thr308) followed by phosphorylation on the hydrophobic motif (Ser473). Studies using overexpression of Akt in vitro and in vivo have implicated the kinase in either attenuating or increasing cardiac hypertrophy, depending on signal intensity and localization of Akt in the cell. Recently the protein phosphatase PHLPP (PH domain leucine-rich repeat protein phosphatase) was shown to dephosphorylate Akt on its hydrophobic motif (Ser473), thereby decreasing kinase activity. We hypothesized that PHLPP could serve as an important regulator of Akt signaling in the heart and that loss of PHLPP would accentuate Akt activation under physiological conditions. We generated phlpp1 null mice to investigate the cardiac phenotype induced by modulating the kinetics of Akt activation in vivo . Myocytes were isolated from PHLPP1 knock-out and wild-type mice to demonstrate loss of PHLPP1 protein and increased Akt phosphorylation following stimulation with the cytokine LIF. Histological examination of hearts revealed that PHLPP1 KO mice have an increased capillary to myocyte ratio compared to age matched wild-type mice at baseline. Increased capillary networks were also detected in the PHLPP1 KO mice relative to wild-type mice using corrosion casting. To determine the role of PHLPP removal on cardiac hypertrophy, PHLPP1 null mice and wild-type mice were subjected to two weeks pressure overload by transverse aortic constriction (TAC). Cardiac hypertrophy was unexpectedly attenuated in PHLPP1 null mice (26% increase in HW/BW ratio vs. 48% in wild-type mice). In contrast, PHLPP1 null mice display an accentuated response to physiological hypertrophy induced by swimming compared to wild-type controls (46% vs. 38% respectively). Our data suggests that there is enhanced Akt activation following PHLPP removal and this attenuates pathological hypertrophy due to changes in capillary density.

The air quality conformity process requires travel speed estimation for a horizon year, where often few roadway characteristics are precisely known. This paper presents the results of a study to validate three relatively common speed estimation techniques comparing predicted speeds with speeds measured on specific roadway links and illustrates how disparity in speed predictions affect nitrogen oxide (NOx) and volatile organic compound (VOC) estimates in the MOBILE6 emissions model. The results are intriguing. On average, the mean absolute errors for the three techniques were similar, ranging between 8 and 12 mph. This large error resulted because free-flow speed and capacity from the long-range model were not always representative of the links being studied. Further, the study suggests that the error associated with any of the techniques could be reduced to 4 mph through judicious altering of the default capacity or default free-flow speed for a given class of links, a feasible approach even for large networks. Finally, MOBILE6 testing with Virginia metropolitan data suggests that the differences in speed predictions yield a 2.5% difference in estimated VOC emissions, with one technique overestimating VOC emissions by 1.75% and two underestimating VOC emissions by 0.71%. All three techniques underestimated metropolitan area NOx emissions by less than 2%. Because link-based speed validation efforts are relatively rare within the conformity analysis process, the methodology discussed here should be of interest to smaller metropolitan planning organizations seeking to verify that accurate speeds are used in conformity determination.

Purcell, Elizabeth M. A.F.R.C.S.I., M.Med.Sci.; Hussain, Mumtaz F.R.C.S.E.; McCann, Jack F.R.C.S.I., B.Sc. Author Information

The acute effects of both untreated and dispersant-treated Prudhoe Bay crude oil on the early life-stages of three marine species were investigated. Identification of which water-accommodated fraction (undispersed or chemically dispersed) was considered "more toxic" was dependent on species, time, and endpoint (and by inference, test protocol). Generally, the data showed that at roughly equivalent hydrocarbon concentrations untreated oil solutions resulted in higher initial effects (< 1 h) in mysid and topsmelt tests, whereas dispersed oil solutions elicited higher levels of larval abnormality in abalone tests and higher levels of mortality in mysid tests. While differences in test protocols existed among the species tested, topsmelt were the most sensitive species to untreated oil solutions, with mysids being most sensitive to dispersed oil solutions.