The Challenge of Educating in a Highly-Connected and Multitasking World

Today’s students are more connected and more integrated with their world than any past generation and information is readily available today from a multitude of sources. To what extent have these advances improved our students’ ability to become learned pharmacy professionals who are informed not only of the current world and its events but the profession itself

Role of the Genomics Revolution in Pharmaceutics

Highlights the examples of Thiopurine S-methyltransferase (TPMT) and Warfarin as a means of describing some of the problems that are common to many pharmacogenetic cases. The pharmacogenetic literature contains many examples of confusing, or even contradictory, studies that arise due to unknown environmental factors that result in poor outcomes; drugs whose metabolism/transport are affected by multiple genes in multiple pathways; and clinically important genes that have many rare allelic variants with similar phenotypes variation in the frequencies of allelic variants among ethnic groups that mask the role of any one variant. These issues are common to most gene/drug dynamics and do not preclude the importance of pharmacogenetic studies. They do call for more realistic assessments of the role of genetic testing for the practicing clinician as this field develops

From Corals To Kidney Transplant Patients – Population Genetic/Genomic Approaches To Diverse Problems

Dr. Daniel Brazeau gives an overview presentation of potential applications for his research in genetics and pharmacogenomics.https://dune.une.edu/biomed_facpres/1001/thumbnail.jp

Genetic Structure in the Coral, Montastraea cavernosa: Assessing Genetic Differentiation among and within Mesophotic Reefs

Mesophotic coral reefs (30–150 m) have recently received increased attention as a potential source of larvae (e.g., the refugia hypothesis) to repopulate a select subset of the shallow water (,30 m) coral fauna. To test the refugia hypothesis we used highly polymorphic Amplified Fragment Length Polymorphism (AFLP) markers as a means to assess small-scale genetic heterogeneity between geographic locations and across depth clines in the Caribbean coral, Montastraea cavernosa. Zooxanthellae-free DNA extracts of coral samples (N = 105) were analyzed from four depths, shallow (3–10 m), medium (15– 25 m), deep (30–50 m) and very deep (60–90 m) from Little Cayman Island (LCI), Lee Stocking Island (LSI), Bahamas and San Salvador (SS), Bahamas which range in distance from 170 to 1,600 km apart. Using AMOVA analysis there were significant differences in WST values in pair wise comparisons between LCI and LSI. Among depths at LCI, there was significant genetic differentiation between shallow and medium versus deep and very deep depths in contrast there were no significant differences in WST values among depths at LSI. The assignment program AFLPOP, however, correctly assigned 95.7% of the LCI and LSI samples to the depths from which they were collected, differentiating among populations as little as 10 to 20 m in depth from one another. Discriminant function analysis of the data showed significant differentiation among samples when categorized by collection site as well as collection depth. FST outlier analyses identified 2 loci under positive selection and 3 under balancing selection at LCI. At LSI 2 loci were identified, both showing balancing selection. This data shows that adult populations of M. cavernosa separated by depths of tens of meters exhibits significant genetic structure, indicative of low population connectivity among and within sites and are not supplying successful recruits to adjacent coral reefs less than 30 m in depth

Genetic Connectivity in Scleractinian Corals across the Northern Gulf of Mexico: Oil/Gas Platforms, and Relationship to the Flower Garden Banks

The 3,000 oil/gas structures currently deployed in the northern Gulf of Mexico (GOM) provide hard substratum for marine organisms in a region where such has been rare since the Holocene. The major exception to this are the Flower Garden Banks (FGB). Corals are known to have colonized oil/gas platforms around the FGB, facilitating biogeographic expansion. We ask the question, what are the patterns of genetic affinity in these coral populations. We sampled coral tissue from populations of two species occurring on oil and gas platforms: Madracis decactis (hermatype) and Tubastraea coccinea (invasive ahermatype). We sampled 28 platforms along four transects from 20 km offshore to the continental shelf edge off 1) Matagorda Island, TX; 2) Lake Sabine, TX; 3) Terrebonne Bay, LA; and 4) Mobile, AL. The entire population of M. decactis was sampled between depths of 5 m and 37 m. T. coccinea populations were sub-sampled. Genetic variation was assessed using the PCR-based Amplified Fragment Length Polymorphisms (AFLPs). Data were analyzed via AFLPOP and STRUCTURE. Genetic connectivity among M. decactis platform populations was highest near the FGB and decreased to the east. Connectivity increased again in the eastern sector, indicating isolation between the populations from different sides of the Mississippi River (Transects 3 and 4). A point-drop in genetic affinity (relatedness) at the shelf edge south of Terrebonne Bay, LA indicated a population differing from all others in the northern GOM. Genetic affinities among T. coccinea were highest in the west and decreased to the east. Very low genetic affinities off Mobile, AL indicated a dramatic difference between those populations and those west of the Mississippi River, apparently a formidable barrier to larval dispersal

Racial Influence on ABCB1 Gene Expression in Peripheral Blood Mononuclear Cells in Stable Renal Transplant Recipients

Background: Immunosuppressive therapy (IT) such as tacrolimus are influenced by pglycoprotein (P-gp) which modulates cellular efflux of this drug. P-gp is present on peripheral mononuclear cells (PBMC) and is encoded by the ABCB1 gene. No data are available regarding the impact of race on ABCB1 gene expression in PBMCs post-transplant over IT dosing interval. Methods: An observational study was completed in 20 African American (AA) and 11 Caucasian (C) stable renal transplant recipients (RTR) (ages 30-74 yrs) receiving tacrolimus (trough: 5 - 10 ng /ml), and enteric coated mycophenolate sodium. At time 0 (prior to IT) & 4, 8 and 12 hours after immunosuppression, PBMCs were collected for ABCB1 gene expression analysis by quantitative real-time-polymerase chain reaction (QRT-PCR). The target ABCB1 gene PCR product was cloned, and verified by sequencing. The cloned ABCB1 gene was used to establish standard curves (linear over 6 orders of magnitude; r 2=0.996) and assess PCR efficiencies. Total ABCB1 copies and normalized copies using Alien RNA were assessed. Results: The normalized (pABCB1 gene expression was higher among Caucasians and at each time until 12 hours. See Table below. Conclusions: The racial differences in ABCB1 gene expression was noted with greater expression in Caucasians than African Americans. These racial differences in ABCB1 gene expression may influence intracellular tacrolimus concentrations mediated by P-gp and affect clinical outcomes relative to African Americans and Caucasianshttps://dune.une.edu/pharmsci_facpost/1000/thumbnail.jp

Open Access: Is OA Ok?

Open Access (OA) publishing is growing exponentially across many disciplines. What do UNE students and faculty need to know about it? UNE Librarian Beth Dyer presents its opportunities and pitfalls, with advice on how to approach OA both as an author and a consumer. UNE College of Pharmacy’s Dr. Dan Brazeau talks about his experiences with OA publishing. UNE Librarian Bethany Kenyon discusses UNE\u27s open access digital repository, DUNE: Digital UNE, where UNE community members can deposit and share original content

Environmental Symbiont Acquisition May Not Be the Solution to Warming Seas for Reef-Building Corals

BACKGROUND: Coral reefs worldwide are in decline. Much of the mortality can be attributed to coral bleaching (loss of the coral's intracellular photosynthetic algal symbiont) associated with global warming. How corals will respond to increasing oceanic temperatures has been an area of extensive study and debate. Recovery after a bleaching event is dependent on regaining symbionts, but the source of repopulating symbionts is poorly understood. Possibilities include recovery from the proliferation of endogenous symbionts or recovery by uptake of exogenous stress-tolerant symbionts. METHODOLOGY/PRINCIPAL FINDINGS: To test one of these possibilities, the ability of corals to acquire exogenous symbionts, bleached colonies of Porites divaricata were exposed to symbiont types not normally found within this coral and symbiont acquisition was monitored. After three weeks exposure to exogenous symbionts, these novel symbionts were detected in some of the recovering corals, providing the first experimental evidence that scleractinian corals are capable of temporarily acquiring symbionts from the water column after bleaching. However, the acquisition was transient, indicating that the new symbioses were unstable. Only those symbiont types present before bleaching were stable upon recovery, demonstrating that recovery was from the resident in situ symbiont populations. CONCLUSIONS/SIGNIFICANCE: These findings suggest that some corals do not have the ability to adjust to climate warming by acquiring and maintaining exogenous, more stress-tolerant symbionts. This has serious ramifications for the success of coral reefs and surrounding ecosystems and suggests that unless actions are taken to reverse it, climate change will lead to decreases in biodiversity and a loss of coral reefs

Sex and Haplotype Associations with Adverse Effects of Calcineurin Inhibitors Post-Renal Transplant

BACKGROUND: P-glycoprotein (P-gp), an ABC transport protein contributes to the interpatient pharmacokinetic and pharmacodynamic variability of calcineurin inhibitors(CNI), tacrolimus(TAC) and cyclosporine (CYA). ABCB1 encodes P-gp and the single nucleotide polymorphisms (SNP) 1236C\u3eT, 2677G\u3eT/A, 3435C\u3eT may alter protein expression or function. Our objective was to examine the association of ABCB1 haplotypes, sex and race with chronic CNI adverse effects (AE) in renal transplant recipients (RTR). METHODS: A meta-analysis of 3 prospective observational studies was completed in 149 stable RTR [GFR= 51 ±17 ml/min/1.73m2] using identical inclusion and exclusion criteria in 62 African Americans (AA) and 81 Caucasians (C) treated with CYA (troughs: 50- 150 ng/ml) and mycophenolate mofetil or TAC (troughs: 5-10 ng/ml) and mycophenolate sodium. Each RTR had AE assessed using standardized objective scales by study physicians. A Cumulative AE ratio was determined using 14 AE. Separate gastrointestinal (GI), central nervous system (CNS), and aesthetic AE ratios were also assessed. DNA from peripheral blood mononuclear cells was collected to characterize ABCB1 SNPs completed on 11/15/12. Haplotype computation and association with AE was completed by THESIAS program on 12/3/12. RESULTS: All genotypes were in Hardy-Weinberg equilibria. AA had a greater frequency of the C-G-C haplotype (SNPs: 1236-2677-3435) compared to C (71.6% vs. 44.2%; p\u3c0.001). A gender difference was noted for Cumulative (p\u3c0.001); GI (p=0.046); aesthetic (p=0.0002) and CNS (p=0.051) AE ratios with greater AE ratios in females. The Aesthetic AE ratio was associated with haplotype T-T-C (p=0.008). Haplotype C-T-T was associated with increased GI AE ratio (p=0.02) though the effect was not significant when sex was included as a covariate (p=0.13). Race had no associations with AE. CONCLUSION: RTR receiving CNI based immunosuppression within the therapeutic range exhibited interpatient variability in AE with associations to sex and ABCB1 haplotypes.https://dune.une.edu/pharmsci_facpost/1001/thumbnail.jp

The use of standardized patients for mock oral board exams in neurology: a pilot study

BACKGROUND: Mock oral board exams, fashioned after the live patient hour of the American Board of Psychiatry and Neurology exam, are commonly part of resident assessment during residency training. Exams using real patients selected from clinics or hospitals are not standardized and do not allow comparisons of resident performance across the residency program. We sought to create a standardized patient mock oral board exam that would allow comparison of residents' clinical performance. METHODS: Three cases were created and then used for this mock oral boards exercise utilizing trained standardized patients. Residents from the University of Cincinnati and Indiana University participated in the exam. Residents were scored by attending physician examiners who directly observed the encounter with the standardized patient. The standardized patient also assessed each resident. A post-test survey was administered to ascertain participant's satisfaction with the examination process. RESULTS: Resident scores were grouped within one standard deviation of the mean, with the exception of one resident who was also subjectively felt to "fail" the exam. In exams with two faculty "evaluators", scores were highly correlated. The survey showed satisfaction with the examination process in general. CONCLUSION: Standardized patients can be used for mock oral boards in the live patient format. Our initial experience with this examination process was positive. Further testing is needed to determine if this examination format is more reliable and valid than traditional methods of assessing resident competency