Uric Acid Directly Promotes Human T-Cell Activation

BackgroundAbnormally high serum uric acid levels have been associated with several disease conditions including gout and kidney stone disease. More recently, it was shown that uric acid crystals stimulate dendritic cell maturation, activate the NALP3 inflammasome, and enhance antigen-specific immune responses. We hypothesize that uric acid can also stimulate T cells directly and in the absence of antigen presentation.MethodsPurified primary human T cells were incubated with and without uric acid at concentrations of 50, 100, 150, and 200 μg/mL. The expression of T-cell activation markers CD25 and CD70 was assessed by flow cytometry. In other experiments, Jurkat T cells were used and the expression of the costimulatory molecule CD70 was determined at the mRNA level.ResultsUric acid directly activates primary human T cells in the absence of antigen presentation. Furthermore, primary human T cells and Jurkat T cells treated with uric acid overexpress the costimulatory molecule CD70, which plays an important role in T cell-B cell interaction and antibody production.ConclusionsThe finding that uric acid directly promotes T-cell activation in an antigen-independent system is novel and might play a mechanistic role in the inflammatory response observed in gouty arthritis and other immune-mediated diseases.     

Defective DNA methylation and CD70 overexpression in CD4+ T cells in MRL/lpr lupus-prone mice

We have determined that abnormal DNA methylation in T cells coincides with the development of autoimmunity, using a mouse model that exhibits an age-dependent lupus-like disease (MRL/lpr mice). Splenic CD4(+) T cells were isolated from these mice at 5 and 16 wk of age (before and after autoimmunity is established) and the expression of DNA methyltransferase 1 (Dnmt1) and the methylation-sensitive gene Tnfsf7 (CD70) was measured. Bisulfite DNA sequencing was used to monitor the methylation status of the Tnfsf7 gene. We found that Dnmt1 steady-state mRNA levels were significantly lower in 16-wk-old MRL/lpr mice, which had established autoimmunity, compared to the 5-wk-old MRL/lpr mice. Furthermore, the expression of CD70 was higher in MRL/lpr mice at 16 wk. CD70 was overexpressed in MRL/lpr mice compared to age- and sex-matched MRL(+/+) controls. Bisulfite DNA sequencing of the Tnfsf7 gene in MRL/lpr mice revealed that at 16 wk, CG pairs were hypomethylated compared to 5-wk-old mice, and that Tnfsf7 from MRL/lpr mice was hypomethylated at 16 wk relative to age-matched MRL(+/+) controls. Our data indicate that decreased expression of Dnmt1 and the corresponding T cell DNA hypomethylation correlate with the development of age-dependent autoimmunity in MRL/lpr mice.     

No One-Size-Fits-All: Sexual Health Education Preferences in Patients with Breast Cancer

Annals of Surgical Oncology - Using explanatory mixed methods, we characterize the education that patients with breast cancer received about potential sexual health effects of treatment and explore...     

The stereotyped behavior scale: psychometric properties and norms

The Stereotyped Behavior Scale (SBS) is an empirically developed behavior rating scale for adolescents and adults with mental retardation (Rojahn, Tassé & Sturmey, 1997). Since the original publication, one item was deleted and two items were merged, leaving 24 items. In an additional change, severity scales were added to the frequency scales. In this paper, psychometric properties and (relative) norms for the new SBS are presented. In the psychometric study, 45 adults with mental retardation from a residential facility participated. Of these, 15 were selected for high-rates or very severe forms of stereotyped behaviors, 15 for mild to moderate rates or less severe stereotypies, and 15 for the low rates or absence of stereotyped behaviors. Direct care staff familiar with the participants completed the SBS and the "Stereotypy" subscale of the Aberrant Behavior Checklist-Residential (ABC-R) (Aman, Singh, Stewart & Field, 1985). For 15 participants, two raters independently completed the SBS. In addition, 45-min direct behavior observations were conducted on 16 participants. After approximately four weeks, the instruments were completed a second time by the same raters. As for reliability, the SBS frequency and severity scale total scores yielded test-retest intraclass coefficients (ICC) of 0.93 and 0.71, ICC interrater agreement of 0.76 and 0.75, and each had an internal consistency a of 0.91. For criterion validity, the SBS frequency and severity scores correlated with the ABC-R "Stereotypy" score at 0.80 and 0.84 (Pearson r), with systematic behavior observations at 0.50 and 0.65 (Pearson r), and with the a priori classification at 0.50 and 0.65 (Spearman p). From a previous data set of 550 individuals with stereotypic behavior, normative data (percentile ranks and T-scores) were derived. The data were presented in two tables, one showing a breakdown of gender by age groups, and the second one of age groups by level of functioning.     

A local exhaust ventilation system to reduce airborne ribavirin concentrations

A local exhaust hood was designed and built to capture and contain aerosol emissions of ribavirin during drug administration. The newly designed over-the-head hood is similar to the single hood currently used to administer the drug. This new hood was surrounded by an exhaust plenum to form a compound hood configuration. The exhaust plenum was connected to a filtered local exhaust air system to remove the waste aerosol. The compound hood and local exhaust ventilation system were evaluated for leak rate and inside hood aerosol concentration as a function of exhaust flow rates. This hood reduced the leak rate from an average of 98% with the traditional head hood to an average of less than 1% with the compound hood with exhaust port. The compound hood did not perform quite as well when not in use (set aside during infant caretaking) with the nebulizer remaining on. The leak rate was found to increase from an average of less than 1% to an average of 12% when trials were conducted that used a doll as a simulated patient versus trials without a doll, respectively. As regards therapeutic dose inside the hood, the system's performance may lead to an 18% to 25% decrease in inside hood concentration of aerosol entering the hood. Optimum hood operating parameters were identified. An exhaust flow rate in the range from 1.0 Lpm below to 1.0 Lpm above inlet flow rate from the small particle aerosol generator (SPAG nebulizer) reduced the leak rate to an average of less than 1%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transient diabetes insipidus in pregnancy complicated by hypertension and seizures

A case is presented of a primigravida with transient diabetes insipidus, gestational hypertension, and multiple seizures resistant to magnesium sulfate and diazepam. After addition of phenytoin, no further seizures occurred. Transient diabetes insipidus in pregnancy has been previously associated with hypertension, liver dysfunction, and fetal distress. Considered with previous cases, it is suggested that seizures may frequently be part of this syndrome.     

Integration of First- and Second-Year Introductory Pharmacy Practice Experiences

Objectives

To describe the integration of a first- and second-year introductory pharmacy practice experience (IPPE) involving direct patient contact in hospitals and clinics as a means of more efficiently using academic and preceptor resources.

Design

Two IPPE courses were integrated in fall 2004 to accomodate increasing enrollment in classes and limited clinical practice sites and preceptors, as well as to meet the increased need for students and clinicians to practice principles of self-education. P1 and P2 students interviewed patients and presented patient cases; preceptor expectations were structured by instructional objectives. Student and preceptor course evaluations were assessed from survey data.

Assessment

During the assessment period, all students passed the courses. Following integration of the IPPEs, both courses received positive evaluations from students and preceptors. Initial advanced pharmacy practice experience (APPE) grades for students completing the courses further suggests that the integrated IPPEs were beneficial to students.

Conclusion

The successful integration of first- and second- year IPPE courses resulted in more efficient use of academic and preceptor resources and created a model for other colleges of pharmacy to consider.     

“I just need to know they are going to do what they say they’re going to do with my mom.” Understanding hospice expectations from the patient,caregiver and admission nurse perspective

Objective

The objective of this paper is to understand patient, caregiver and hospice admission nurses needs during the hospice admission conversation so patients and their caregivers can make informed decisions about hospice.

Keeping the patient in the center: Common challenges in the practice of shared decision making

Objective

To examine situations where shared decision making (SDM) in practice does not achieve the goal of a patient-centered decision.