Potential for TCDD to induce regulatory functions in B cells as part of the mechanism for T cell suppression in EAE.

Part of the mechanism by which 2,3,7.8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses immune function involves induction of regulatory T cells and suppression of effector T cells. The goal of this project was to examine whether TCDD's suppression of effector T cells was due in part to inducing B regulatory cells (Bregs). TCDD's potential to increase the percentage and/or function of CD24+CD38+ B cells was assessed in response to lipopolysaccharide (LPS) + interleukin (IL)-4 in vitro and in a mild model of experimental autoimmune encephalomyelitis (EAE) in vivo. In vitro, TCDD did not consistently increase the percentage of CD19+CD24+CD38+ cells using splenocytes, purified B cells or bone marrow (BM) cells. However, TCDD increased IL-10 in all three culture preparations, and TCDD increased the percentage of CD5+CD24+CD38+ cells producing IL-10. In EAE, TCDD did not affect the percentage of the CD24+CD38+ cell population in CD19, B220 or CD5 B cells in splenocytes (SPLC), lymph nodes (LN) nor BM cells at end-stage disease. On the other hand, TCDD increased the CD19+CD24+CD38+ percentage in the spinal cord (SC) in EAE. Moreover, TCDD-treated B cells isolated from spleens or TCDD-treated BM cells in EAE mice modestly reduced the ability of naïve effector T cells to express interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Together these data show that TCDD can induce regulatory functions in B cells, although it was not obvious simply by examining the expression of regulatory markers but by assessing function by cytokine production or mixed lymphocyte responses.

Changes in Health and Ability to Work Among Medicaid Expansion Enrollees: a Mixed Methods Study.

BACKGROUND: Michigan expanded Medicaid under the Affordable Care Act (Healthy Michigan Plan [HMP]) to improve the health of low-income residents and the state's economy. OBJECTIVE: To understand HMP's impact on enrollees' health, ability to work, and ability to seek employment DESIGN: Mixed methods study, including 67 qualitative interviews and 4090 computer-assisted telephone surveys (response rate 53.7%) PARTICIPANTS: Non-elderly adult HMP enrollees MAIN MEASURES: Changes in health status, ability to work, and ability to seek employment KEY RESULTS: Half (47.8%) of respondents reported better physical health, 38.2% better mental health, and 39.5% better dental health since HMP enrollment. Among employed respondents, 69.4% reported HMP helped them do a better job at work. Among out-of-work respondents, 54.5% agreed HMP made them better able to look for a job. Among respondents who changed jobs, 36.9% agreed HMP helped them get a better job. In adjusted analyses, improved health was associated with the ability to do a better job at work (aOR 4.08, 95% CI 3.11-5.35, p < 0.001), seek a job (aOR 2.82, 95% CI 1.93-4.10, p < 0.001), and get a better job (aOR 3.20, 95% CI 1.69-6.09, p < 0.001), but not with employment status (aOR 1.08, 95% CI 0.89-1.30, p = 0.44). In interviews, several HMP enrollees attributed their ability to get or maintain employment to improved physical, mental, and dental health because of services covered by HMP. Remaining barriers to work cited by enrollees included older age, disability, illness, and caregiving responsibilities. CONCLUSIONS: Many low-income HMP enrollees reported improved health, ability to work, and job seeking after obtaining health insurance through Medicaid expansion.

TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro.

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is a ligand for the aryl hydrocarbon receptor (AhR). TCDD is well-characterized to produce immunotoxicity, including suppression of antibody production. Previously we showed that TCDD inhibited myelin oligodendrocyte glycoprotein (MOG) peptide-specific IgG and attenuated disease in experimental autoimmune encephalomyelitis (EAE) model in mice. Thus, the purpose of this study was to characterize the effects of TCDD on IgG subclasses in EAE and in vitro and assess effects in B cells derived from various tissues. TCDD modestly suppressed intracellular IgG expression in splenocytes (SPLC), but not bone marrow (BM) or lymph node (LN) cells. To further understand TCDD's effects on IgG, we utilized LPS and LPS + IL-4 in vitro to stimulate IgG3 and IgG1 production, respectively. TCDD preferentially suppressed IgG1+ cell surface expression, especially in SPLC. However, TCDD was able to suppress IgG1 and IgG3 secretion from SPLC and B cells, but not BM cells. Lastly, we revisited the EAE model and determined that TCDD suppressed MOG-specific IgG1 production. Together these data show that the IgG1 subclass of IgG is a sensitive target of suppression by TCDD. Part of the pathophysiology of EAE involves production of pathogenic antibodies that can recruit cytolytic cells to destroy MOG-expressing cells that comprise myelin, so inhibition of IgG1 likely contributes to TCDD's EAE disease attenuation.

Adverse drug reaction and medication error reporting by pharmacy students.

BACKGROUND: The reporting of adverse drug reactions (ADRs) and medication errors is the responsibility of all who are involved, particularly pharmacists. Since pharmacists are often privy to information surrounding ADRs and medication errors, it is of utmost importance that they are educated regarding the procedures of reporting. OBJECTIVE: To determine pharmacy students' knowledge of and ability to report ADRs and medication errors. METHODS: A total of 1322 students from 9 colleges of pharmacy were surveyed. RESULTS: The largest group of respondents was fifth-year pharmacy students (38%) followed by third-, fourth-, and sixth-year students (28%, 26%, and 8%, respectively). The majority of students reported learning about ADR and medication error reporting programs via didactic experiences. In comparison, fewer students cited alternative mechanisms of learning, including experiential rotations and work experience. Overall, respondents demonstrated the most experience with MedWatch and the least experience with the Vaccine Adverse Event Reporting System (VAERS). As students progressed through pharmacy curricula, there was a positive trend in the ability to locate and complete MedWatch forms. For VAERS and Medication Error Reporting (MER) program forms, however, this positive trend was broken at year 4. For all programs, significantly fewer students demonstrated appropriate use of the forms compared with those indicating familiarity with the programs. CONCLUSIONS: This study demonstrated that students are becoming familiar with ADR and MER programs via the college curriculum; however, there is opportunity for greater exposure and understanding. Colleges of pharmacy should continually seek methods to strengthen the education provided to pharmacy students regarding these programs.