Student perspectives on a collaborative international doctorate of pharmacy program

Objectives: To evaluate the educational experience and teaching methods of the collaborative Doctorate of Pharmacy (PharmD) program between the University of Malta (UM) and the University of Illinois at Chicago (UIC). Methods: A 41-question survey was developed to identify student demographics, satisfaction with the PharmD program and the utility of the current curricular components. Students who enrolled in the program in May 2017 were invited to participate. The survey contained open-ended, 5-point Likert, and multiple-choice type questions. The primary outcomes were the overall satisfaction and student motivations for pursuing the program. Secondary outcomes included the level of difficulty of courses, evaluation of assessment methods, and confidence in an interdisciplinary team. Results: Thirty-six students completed the survey (a response rate of 83.7%). The mean age was 30.1 ± 7.9 years. The majority of the students pursued the PharmD program to improve their knowledge, skills, and opportunity for obtaining a clinical position. The mean overall satisfaction of the program was 3.81 ± 1.1 (5 = very satisfied). Among the core courses, Pharmacotherapeutics had the highest overall satisfaction (4.45 ± 0.91) and level of difficulty (3.84 ± 0.51). Students felt that the tutorials/recitation case discussion sessions were the most effective teaching method (48.4%) and ranked faculties conducting case-based lectures highest for overall performance. Most students felt somewhat confident (54.8%) for participating in a multidisciplinary team. Conclusions: The UM/UIC PharmD Program is a unique program, utilizing a hybrid model of teaching, including distance education, to expose students to a broad and challenging curriculum in clinical pharmacy practice. Students are satisfied with this collaborative, international postgraduate PharmD program.peer-reviewe

Pharmacist-led olaparib follow-up service for ambulatory ovarian cancer patients: A prospective study in a tertiary specialized cancer hospital in China

Purpose: To establish a pharmacist-led olaparib follow-up program for ovarian cancer patients, provide patient education, get information on adverse drug reactions (ADRs), and identify and manage drug-related problems.Methods: Ambulatory adult patients with ovarian cancer receiving olaparib were enrolled. At least one follow-up session was conducted by clinical pharmacists. Pharmacists collected data on the type and grade of ADRs, drug adherence, olaparib dosing, concomitant medications, and pharmacists’ suggestions.Results: 83 patients were enrolled with the median age of 58. The average number of the follow-up sessions provided to each patient was 1.31, and the average duration of each follow-up was 17.78 min. The olaparib starting dose for most patients (97.59%) was 600 mg/d. 36.14% of the patients had missed olaparib doses and 27.71% of the patients had dose adjustments due to ADRs. The most common ADRs (incidence≥10%) were: fatigue (40.96%), anemia (36.14%), leukopenia (36.14%), nausea (28.92%), thrombocytopenia (16.87%), anorexia (16.87%), dyspepsia (15.66%). The tolerability profiles were generally similar between patients treated for “first-line maintenance” and those treated for “recurrence maintenance” (p > .05). There were 42% of the patients who were concomitantly taking medications without exact chemical contents (such as formulated Chinese medicines and Chinese decoctions), and common types of concomitant medications with exact drug names were antihypertensive, anti-hyperglycemic, and anti-hyperlipidemic medications. The pharmacists identified 4 clinically significant drug-drug interactions (DDIs) in two patients. Pharmacists made 196 suggestions mainly related to rational use of the medications and management of ADRs.Conclusion: The study provides the first report about pharmacist-led follow-up service for olaparib. The types of ADRs were similar to those previously observed in clinical trials, and the profiles of ADRs in different types of patients (first-line maintenance vs. recurrence maintenance) were also similar. Pharmacists identified drug-related problems (such as adherence, DDIs and management of ADRs) and offer suggestions for the patients

Molecular network analysis of phosphotyrosine and lipid metabolism in hepatic PTP1b deletion mice

Metabolic syndrome describes a set of obesity-related disorders that increase diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase 1b (PTP1b) deletion mice (L-PTP1b[superscript −/−]) suggest that hepatic PTP1b inhibition would mitigate metabolic-syndrome through amelioration of hepatic insulin resistance, endoplasmic-reticulum stress, and whole-body lipid metabolism. However, the altered molecular-network states underlying these phenotypes are poorly understood. We used mass spectrometry to quantify protein-phosphotyrosine network changes in L-PTP1b[superscript −/−] mouse livers relative to control mice on normal and high-fat diets. We applied a phosphosite-set-enrichment analysis to identify known and novel pathways exhibiting PTP1b- and diet-dependent phosphotyrosine regulation. Detection of a PTP1b-dependent, but functionally uncharacterized, set of phosphosites on lipid-metabolic proteins motivated global lipidomic analyses that revealed altered polyunsaturated-fatty-acid (PUFA) and triglyceride metabolism in L-PTP1b[superscript −/−] mice. To connect phosphosites and lipid measurements in a unified model, we developed a multivariate-regression framework, which accounts for measurement noise and systematically missing proteomics data. This analysis resulted in quantitative models that predict roles for phosphoproteins involved in oxidation–reduction in altered PUFA and triglyceride metabolism.Pfizer Inc. (grant)National Institutes of Health (U.S.) (grant 5R24DK090963)National Institutes of Health (U.S.) (grant U54-CA112967)National Institutes of Health (U.S.) (grant CA49152 R37)National Institutes of Health (U.S.) (grant R01-DK080756)National Mouse Metabolic Phenotyping Center at UMASS (Grant (U24-DK093000))National Science Foundation (U.S.) (Graduate Research Fellowship

The PARP inhibitor AZD2461 provides insights into the role of PARP3 inhibition for both synthetic lethality and tolerability with chemotherapy in preclinical models

The PARP inhibitor AZD2461 was developed as a next-generation agent following olaparib, the first PARP inhibitor approved for cancer therapy. In BRCA1-deficient mouse models, olaparib resistance predominantly involves overexpression of P-glycoprotein,so AZD2461 was developed as a poor substrate for drug transporters. Here we demonstrate the efficacy of this compound against olaparib-resistant tumors that overexpress P-glycoprotein. In addition, AZD2461 was better tolerated in combination with chemotherapy than olaparib in mice, which suggests that AZD2461 could have significant advantages over olaparib in the clinic. However, this superior toxicity profile did not extend to rats. Investigations of this difference revealed a differential PARP3 inhibitory activity for each compound and a higher level of PARP3 expression in bone marrow cells from mice as compared with rats and humans. Our findings have implications for the use of mouse models to assess bone marrow toxicity for DNA-damaging agents and inhibitors of the DNA damage response. Finally, structural modeling of the PARP3-active site with different PARP inhibitors also highlights the potential to develop compounds with different PARP family member specificity profiles for optimal antitumor activity and tolerability

JAK2/IDH-mutant–driven myeloproliferative neoplasm is sensitive to combined targeted inhibition

Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are associated with poor outcomes. Here, we showed that combined expression of Jak2V617Fand mutant IDH1R132Hor Idh2R140Q induces MPN progression, alters stem/progenitor cell function, and impairs differentiation in mice. Jak2V617FIdh2R140Q–mutant MPNs were sensitive to small-molecule inhibition of IDH. Combined inhibition of JAK2 and IDH2 normalized the stem and progenitor cell compartments in the murine model and reduced disease burden to a greater extent than was seen with JAK inhibition alone. In addition, combined JAK2 and IDH2 inhibitor treatment also reversed aberrant gene expression in MPN stem cells and reversed the metabolite perturbations induced by concurrent JAK2 and IDH2 mutations. Combined JAK2 and IDH2 inhibitor therapy also showed cooperative efficacy in cells from MPN patients with both JAK2mutand IDH2mutmutations. Taken together, these data suggest that combined JAK and IDH inhibition May offer a therapeutic advantage in this high-risk MPN subtype.Damon Runyon Cancer Research Foundation (DRG-2241-15)Howard Hughes Medical Institute (Faculty Scholars Award)Stand Up To CancerNational Cancer Institute (U.S.) (P50CA165962)National Cancer Institute (U.S.) (P30CA14051)Koch Institute for Integrative Cancer Research ( Dana-Farber Harvard Cancer Center Bridge Project)Leukemia & Lymphoma Society of America. Specialized Center of Research (SCOR) ProgramNational Institutes of Health (U.S.) (grant U54OD020355-01)National Institutes of Health (U.S.) (grant NCI R01CA172636)National Institutes of Health (U.S.) (grant R35CA197594)National Cancer Institute (U.S.) (Cancer Center Support Grant (P30 CA008747)

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics