Lipids in xylem sap of woody plants across the angiosperm phylogeny.

Lipids have been observed attached to lumen-facing surfaces of mature xylem conduits of several plant species, but there has been little research on their functions or effects on water transport, and only one lipidomic study of the xylem apoplast. Therefore, we conducted lipidomic analyses of xylem sap from woody stems of seven plants representing six major angiosperm clades, including basal magnoliids, monocots and eudicots, to characterize and quantify phospholipids, galactolipids and sulfolipids in sap using mass spectrometry. Locations of lipids in vessels of Laurus nobilis were imaged using transmission electron microscopy and confocal microscopy. Xylem sap contained the galactolipids di- and monogalactosyldiacylglycerol, as well as all common plant phospholipids, but only traces of sulfolipids, with total lipid concentrations in extracted sap ranging from 0.18 to 0.63 nmol ml-1 across all seven species. Contamination of extracted sap from lipids in cut living cells was found to be negligible. Lipid composition of sap was compared with wood in two species and was largely similar, suggesting that sap lipids, including galactolipids, originate from cell content of living vessels. Seasonal changes in lipid composition of sap were observed for one species. Lipid layers coated all lumen-facing vessel surfaces of L. nobilis, and lipids were highly concentrated in inter-vessel pits. The findings suggest that apoplastic, amphiphilic xylem lipids are a universal feature of angiosperms. The findings require a reinterpretation of the cohesion-tension theory of water transport to account for the effects of apoplastic lipids on dynamic surface tension and hydraulic conductance in xylem.

Lipidomic Analysis of Arabidopsis T-DNA Insertion Lines Leads to Identification and Characterization of C-Terminal Alterations in FATTY ACID DESATURASE 6.

Mass-spectrometry-based screening of lipid extracts of wounded and unwounded leaves from a collection of 364 Arabidopsis thaliana T-DNA insertion lines produced lipid profiles that were scored on the number and significance of their differences from the leaf lipid profiles of wild-type plants. The analysis identified Salk_109175C, which displayed alterations in leaf chloroplast glycerolipid composition, including a decreased ratio between two monogalactosyldiacylglycerol (MGDG) molecular species, MGDG(18:3/16:3) and MGDG(18:3/18:3). Salk_109175C has a confirmed insertion in the At5g64790 locus; the insertion did not co-segregate with the recessive lipid phenotype in the F2 generation of a wild-type (Columbia-0) × Salk_109175C cross. The altered lipid compositional phenotype mapped to the At4g30950 locus, which encodes the plastidial ω-6 desaturase FATTY ACID DESATURASE 6 (FAD6). Sequencing revealed a splice-site mutation, leading to the in-frame deletion of 13 amino acids near the C-terminal end of the 448 amino acid protein. Heterologous expression in yeast showed that this deletion eliminates desaturase activity and reduces protein stability. Sequence comparison across species revealed that several amino acids within the deletion are conserved in plants and cyanobacteria. Individual point mutations in four conserved residues resulted in 77-97% reductions in desaturase activity, while a construct with all four alanine substitutions lacked activity. The data suggest that the deleted region of FAD6, which is on the C-terminal side of the four putative transmembrane segments and the histidine boxes putatively involved in catalysis, is critical for FAD6 function.

Teaching and learning under COVID-19 public health edicts: the role of household lockdowns and prior technology usage.

Public health edicts necessitated by COVID-19 prompted a rapid pivot to remote online teaching and learning. Two major consequences followed: households became students' main learning space, and technology became the sole medium of instructional delivery. We use the ideas of "digital disconnect" and "digital divide" to examine, for students and faculty, their prior experience with, and proficiency in using, learning technology. We also explore, for students, how household lockdowns and digital capacity impacted learning. Our findings are drawn from 3806 students and 283 faculty instructors from nine higher education institutions across Asia, Australia, Europe, and North America. For instructors, we find little evidence of a digital divide but some evidence of a digital disconnect. However, neither made a difference to self-reported success in transitioning courses. Faculty instructors were impacted in a myriad of diverse ways. For students, we show that closure and confinement measures which created difficult living situations were associated with lower levels of confidence in learning. The digital divide that did exist among students was less influential than were household lockdown measures in undermining student learning.

Cognitive apprenticeship in health sciences education: a qualitative review.

Cognitive apprenticeship theory emphasizes the process of making expert thinking "visible" to students and fostering the cognitive and meta-cognitive processes required for expertise. The purpose of this review was to evaluate the use of cognitive apprenticeship theory with the primary aim of understanding how and to what extent the theory has been applied to the design, implementation, and analysis of education in the health sciences. The initial search yielded 149 articles, with 45 excluded because they contained the term "cognitive apprenticeship" only in reference list. The remaining 104 articles were categorized using a theory talk coding scheme. An in depth qualitative synthesis and review was conducted for the 26 articles falling into the major theory talk category. Application of cognitive apprenticeship theory tended to focus on the methods dimension (e.g., coaching, mentoring, scaffolding), with some consideration for the content and sociology dimensions. Cognitive apprenticeship was applied in various disciplines (e.g., nursing, medicine, veterinary) and educational settings (e.g., clinical, simulations, online). Health sciences education researchers often used cognitive apprenticeship to inform instructional design and instrument development. Major recommendations from the literature included consideration for contextual influences, providing faculty development, and expanding application of the theory to improve instructional design and student outcomes. This body of research provides critical insight into cognitive apprenticeship theory and extends our understanding of how to develop expert thinking in health sciences students. New research directions should apply the theory into additional aspects of health sciences educational research, such as classroom learning and interprofessional education.

Wheat leaf lipids during heat stress: I. High day and night temperatures result in major lipid alterations.

Understanding how wheat (Triticum aestivum L.) plants under high temperature (HT) regulate lipid composition is critical to developing climate-resilient varieties. We measured 165 glycerolipids and sterol derivatives under optimum and high day and night temperatures in wheat leaves using electrospray ionization-tandem mass spectrometry. Levels of polar lipid fatty acyl chain unsaturation were lower in both heat-tolerant genotype Ventnor and susceptible genotype Karl 92 under HT, compared with optimum temperature. The lower unsaturation was predominantly because of lower levels of 18:3 acyl chains and higher levels of 18:1 and 16:0 acyl chains. Levels of 18:3-containing triacylglycerols increased threefold/more under HT, consistent with their possible role in sequestering fatty acids during membrane lipid remodelling. Phospholipids containing odd-numbered or oxidized acyl chains accumulated in leaves under HT. Sterol glycosides (SG) and 16:0-acylated sterol glycosides (ASG) were higher under HT than optimum temperatures. Ventnor had lower amounts of phospholipids with oxidized acyl chains under HT and higher amounts of SG and 16:0-ASG than Karl 92. Taken together, the data demonstrate that wheat leaf lipid composition is altered by HT, in which some lipids are particularly responsive to HT, and that two wheat genotypes, chosen for their differing physiological responses to HT, differ in lipid profile under HT.

Left Ventricular Dysfunction After Treatment With Ipilimumab for Metastatic Melanoma.

Ipilimumab is a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) that is approved by the US Food and Drug Administration for the treatment of unresectable or metastatic melanoma. Ipilimumab is known to cause immune-mediated adverse reactions because of the resultant increase in T-cell activity. To date, there are no published reports of ipilimumab-related heart failure, although a recently published report describes a case of transient cardiomyopathy associated with its use. We report the case of a 60-year-old man who developed left ventricular dysfunction with an asymptomatic reduction in ejection fraction from 55%-60% at baseline to 40%-45% 4 months after completing a second course of treatment with ipilimumab for metastatic melanoma. Ipilimumab was not restarted, and the patient was initiated on lisinopril and carvedilol. Repeat echocardiograms 3 and 5 months later revealed ejection fractions of 40%-45% and 55%-60%, respectively.

Quantitative profiling and pattern analysis of triacylglycerol species in Arabidopsis seeds by electrospray ionization mass spectrometry.

Plant triacylglycerols (TAGs), or vegetable oils, provide approximately 25% of dietary calories to humans and are becoming an increasingly important source of renewable bioenergy and industrial feedstocks. TAGs are assembled by multiple enzymes in the endoplasmic reticulum from building blocks that include an invariable glycerol backbone and variable fatty acyl chains. It remains a challenge to elucidate the mechanism of synthesis of hundreds of different TAG species in planta. One reason is the lack of an efficient analytical approach quantifying individual molecular species. Here we report a rapid and quantitative TAG profiling approach for Arabidopsis seeds based on electrospray ionization tandem mass spectrometry with direct infusion and multiple neutral loss scans. The levels of 93 TAG molecular species, identified by their acyl components, were determined in Arabidopsis seeds. Quantitative TAG pattern analyses revealed that the TAG assembly machinery preferentially produces TAGs with one elongated fatty acid. The importance of the selectivity in oil synthesis was consistent with an observation that an Arabidopsis mutant overexpressing a patatin-like phospholipase had enhanced seed oil content with elongated fatty acids. This quantitative TAG profiling approach should facilitate investigations aimed at understanding the biochemical mechanisms of TAG metabolism in plants.

Lipid changes after leaf wounding in Arabidopsis thaliana: expanded lipidomic data form the basis for lipid co-occurrence analysis.

A direct-infusion electrospray ionization triple-quadrupole mass spectrometry method with multiple reaction monitoring (MRM) was employed to measure 264 lipid analytes extracted from leaves of Arabidopsis thaliana subjected to mechanical wounding. The method provided precise measurements with an average coefficient of variation of 6.1%. Lipid classes analyzed comprised galactolipids and phospholipids (including monoacyl molecular species, molecular species with oxidized acyl chains, phosphatidic acids (PAs)), tri- and tetra-galactosyldiacylglycerols (TrGDGs and TeGDGs), head-group-acylated galactolipids, and head-group-acylated phosphatidylglycerol (acPG), sulfoquinovosyldiacylglycerols (SQDGs), sphingolipids, di- and tri-acylglycerols (DAGs and TAGs), and sterol derivatives. Of the 264 lipid analytes, 254 changed significantly in response to wounding. In general, levels of structural lipids decreased, whereas monoacyl molecular species, galactolipids and phosphatidylglycerols (PGs) with oxidized fatty acyl chains, PAs, TrGDGs, TeGDGs, TAGs, head-group-acylated galactolipids, acPG, and some sterol derivatives increased, many transiently. The observed changes are consistent with activation of lipid oxidizing, hydrolyzing, glycosylating, and acylating activities in the wounding response. Correlation analysis of the levels of lipid analytes across individual control and treated plants was used to construct a lipid dendrogram and to define clusters and sub-clusters of lipid analytes, each composed of a group of lipids which occurred in a coordinated manner. Current knowledge of metabolism supports the notion that observed sub-clusters comprise lipids generated by a common enzyme and/or metabolically downstream of a common enzyme. This work demonstrates that co-occurrence analysis, based on correlation of lipid levels among plants, is a powerful approach to defining lipids generated in vivo by a common enzymatic pathway.

Biosynthetic labeling and two-color imaging of phospholipids in cells.

Phospholipids with a choline head group are abundant components of all biological membranes, performing critical functions in cellular structure, metabolism, and signaling. In spite of their importance, our ability to visualize choline phospholipids in vivo remains very limited. We present a simple and robust chemical strategy to image choline phospholipids, based on the metabolic incorporation of azidocholine analogues, that accurately reflects the normal biosynthetic incorporation of choline into cellular phospholipids. Azidocholine-labeled phospholipids can be imaged in cells with high sensitivity and resolution, following derivatization with fluorophores, by bio-orthogonal chemical reactions compatible with live-cell imaging. We used this method to visualize the subcellular localization of choline phospholipids. We also demonstrate that double metabolic labeling with azidocholine and propargylcholine allows sensitive two-color imaging of choline phospholipids. Our method represents a powerful approach to directly image phospholipids, and to study their dynamics in cells and tissues.

Student experiences across multiple flipped courses in a single curriculum.

CONTEXT: The flipped classroom approach has garnered significant attention in health professions education, which has resulted in calls for curriculum-wide implementations of the model. However, research to support the development of evidence-based guidelines for large-scale flipped classroom implementations is lacking. OBJECTIVES: This study was designed to examine how students experience the flipped classroom model of learning in multiple courses within a single curriculum, as well as to identify specific elements of flipped learning that students perceive as beneficial or challenging. METHODS: A qualitative analysis of students' comments (n = 6010) from mid-course and end-of-course evaluations of 10 flipped courses (in 2012-2014) was conducted. Common and recurring themes were identified through systematic iterative coding and sorting using the constant comparison method. Multiple coders, agreement through consensus and member checking were utilised to ensure the trustworthiness of findings. RESULTS: Several themes emerged from the analysis: (i) the perceived advantages of flipped learning coupled with concerns about implementation; (ii) the benefits of pre-class learning and factors that negatively affect these benefits, such as quality and quantity of learning materials, as well as overall increase in workload, especially in the context of multiple concurrent flipped courses; (iii) the role of the instructor in the flipped learning environment, particularly in engaging students in active learning and ensuring instructional alignment, and (iv) the need for assessments that emphasise the application of knowledge and critical thinking skills. CONCLUSIONS: Analysis of data from 10 flipped courses provided insight into common patterns of student learning experiences specific to the flipped learning model within a single curriculum. The study points to the challenges associated with scaling the implementation of the flipped classroom across multiple courses. Several core elements critical to the effective design and implementation of the flipped classroom model are identified.

ALOX12 in human toxoplasmosis.

ALOX12 is a gene encoding arachidonate 12-lipoxygenase (12-LOX), a member of a nonheme lipoxygenase family of dioxygenases. ALOX12 catalyzes the addition of oxygen to arachidonic acid, producing 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can be reduced to the eicosanoid 12-HETE (12-hydroxyeicosatetraenoic acid). 12-HETE acts in diverse cellular processes, including catecholamine synthesis, vasoconstriction, neuronal function, and inflammation. Consistent with effects on these fundamental mechanisms, allelic variants of ALOX12 are associated with diseases including schizophrenia, atherosclerosis, and cancers, but the mechanisms have not been defined. Toxoplasma gondii is an apicomplexan parasite that causes morbidity and mortality and stimulates an innate and adaptive immune inflammatory reaction. Recently, it has been shown that a gene region known as Toxo1 is critical for susceptibility or resistance to T. gondii infection in rats. An orthologous gene region with ALOX12 centromeric is also present in humans. Here we report that the human ALOX12 gene has susceptibility alleles for human congenital toxoplasmosis (rs6502997 [P, <0.000309], rs312462 [P, <0.028499], rs6502998 [P, <0.029794], and rs434473 [P, <0.038516]). A human monocytic cell line was genetically engineered using lentivirus RNA interference to knock down ALOX12. In ALOX12 knockdown cells, ALOX12 RNA expression decreased and levels of the ALOX12 substrate, arachidonic acid, increased. ALOX12 knockdown attenuated the progression of T. gondii infection and resulted in greater parasite burdens but decreased consequent late cell death of the human monocytic cell line. These findings suggest that ALOX12 influences host responses to T. gondii infection in human cells. ALOX12 has been shown in other studies to be important in numerous diseases. Here we demonstrate the critical role ALOX12 plays in T. gondii infection in humans.

Patatin-related phospholipase pPLAIIIδ increases seed oil content with long-chain fatty acids in Arabidopsis.

The release of fatty acids from membrane lipids has been implicated in various metabolic and physiological processes, but in many cases, the enzymes involved and their functions in plants remain unclear. Patatin-related phospholipase As (pPLAs) constitute a major family of acyl-hydrolyzing enzymes in plants. Here, we show that pPLAIIIδ promotes the production of triacylglycerols with 20- and 22-carbon fatty acids in Arabidopsis (Arabidopsis thaliana). Of the four pPLAIIIs (α, ß, γ, δ), only pPLAIIIδ gene knockout results in a decrease in seed oil content, and pPLAIIIδ is most highly expressed in developing embryos. The overexpression of pPLAIIIδ increases the content of triacylglycerol and 20- and 22-carbon fatty acids in seeds with a corresponding decrease in 18-carbon fatty acids. Several genes in the glycerolipid biosynthetic pathways are up-regulated in pPLAIIIδ-overexpressing siliques. pPLAIIIδ hydrolyzes phosphatidylcholine and also acyl-coenzyme A to release fatty acids. pPLAIIIδ-overexpressing plants have a lower level, whereas pPLAIIIδ knockout plants have a higher level, of acyl-coenzyme A than the wild type. Whereas seed yield decreases in transgenic plants that ubiquitously overexpress pPLAIIIδ, seed-specific overexpression of pPLAIIIδ increases seed oil content without any detrimental effect on overall seed yield. These results indicate that pPLAIIIδ-mediated phospholipid turnover plays a role in fatty acid remodeling and glycerolipid production.

Prevalent but moderate variation across small geographic regions in patient nonadherence to evidence-based preventive therapies in older adults after acute myocardial infarction.

BACKGROUND: Patient long-term adherence to ß-blockers, HMG-CoA reductase inhibitors (statins), and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) after acute myocardial infarction (AMI) is alarmingly low. It is unclear how prevalent patient adherence may be across small geographic areas and whether this geographic prevalence may vary. METHODS: This is a retrospective cohort study using Medicare service claims files from 2007 to 2009 with Medicare beneficiaries 65 years and above who were alive 30 days after the index AMI hospitalization between January 1, 2008 and December 31, 2008 (N=85,017). The adjusted proportions of patients adherent to ß-blockers, statins, and ACEIs/ARBs, respectively, in the 12 months after discharge across the 306 Hospital Referral Regions (HRRs) were measured and compared by control chart. The intracluster correlation coefficient (ICC) and the additional prediction power from this small-area variation on individual patient adherence were assessed. RESULTS: The adjusted proportion of patients adherent across HRRs ranged from 58% to 74% (median, 66%) for ß-blockers, from 57% to 67% (median, 63%) for ACEIs/ARBs, and from 58% to 73% (median, 66%) for statins. The ICC was 0.053 (95% CI, 0.043-0.064) for ß-blockers, 0.050 (95% CI, 0.039-0.061) for ACEIs/ARBs, and 0.041 (95% CI, 0.031-0.052) for statins. The adjusted proportion of patients adherent across HRRs increased the c-statistic by 0.01-0.02 (P < 0.0001). CONCLUSIONS: Nonadherence to evidence-based preventive therapies post-AMI among older adults was prevalent across small geographic regions. Moderate small-area variation in patient adherence exists.

Enhancing Quality in Psychiatry with Psychiatrists (EQUIPP)--results from a pilot study.

OBJECTIVES: To pilot a pharmacist-led, patient centered medication management program. DESIGN: Prospective, single arm trial. SETTING: Academic geriatric psychiatry outpatient clinic. PARTICIPANTS: Outpatients at least 65 years old, proxy available if demented, and on two or more psychiatric medications. INTERVENTION: A clinical pharmacist completed a baseline medication review and made evidence-based recommendations that were implemented by the pharmacist after discussion with the physician. The pharmacist made a minimum of monthly contact for 6 months to review medications and related issues. MEASUREMENTS: The primary outcome was the change in number of medication related problems over time (3 and 6 months) as defined by a predetermined classification system. RESULTS: The mean age of the 27 patients was 75 years, 10 of whom required a proxy to participate. On average, patients had nine chronic conditions and were taking 14 medications. The mean number (SD; range) of medication related problems at baseline was 4.1 (2.2; 0-8) and at 3 and 6 months were 3.6 (2.4, 0-9) and 3.4 (2.1; 0-8), respectively. Most follow-up problems were new (80% and 89% at 3 and 6 months, respectively). CONCLUSION: Using a pharmacist to deliver a medication management program was feasible and addressed existing problems. New problems, however, developed over a short interval (3-6 months), suggesting that ongoing intervention is required.

Head-group acylation of monogalactosyldiacylglycerol is a common stress response, and the acyl-galactose acyl composition varies with the plant species and applied stress.

Formation of galactose-acylated monogalactosyldiacylglycerols has been shown to be induced by leaf homogenization, mechanical wounding, avirulent bacterial infection and thawing after snap-freezing. Here, lipidomic analysis using mass spectrometry showed that galactose-acylated monogalactosyldiacylglycerols, formed in wheat (Triticum aestivum) and tomato (Solanum lycopersicum) leaves upon wounding, have acyl-galactose profiles that differ from those of wounded Arabidopsis thaliana, indicating that different plant species accumulate different acyl-galactose components in response to the same stress. Additionally, the composition of the acyl-galactose component of Arabidopsis acMGDG (galactose-acylated monogalactosyldiacylglycerol) depends on the stress treatment. After sub-lethal freezing treatment, acMGDG contained mainly non-oxidized fatty acids esterified to galactose, whereas mostly oxidized fatty acids accumulated on galactose after wounding or bacterial infection. Compositional data are consistent with acMGDG being formed in vivo by transacylation with fatty acids from digalactosyldiacylglycerols. Oxophytodienoic acid, an oxidized fatty acid, was more concentrated on the galactosyl ring of acylated monogalactosyldiacylglycerols than in galactolipids in general. Also, oxidized fatty acid-containing acylated monogalactosyldiacylglycerols increased cumulatively when wounded Arabidopsis leaves were wounded again. These findings suggest that, in Arabidopsis, the pool of galactose-acylated monogalactosyldiacylglycerols may serve to sequester oxidized fatty acids during stress responses.

Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.

Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5⁺ stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5⁺ stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking ß-catenin-mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5⁺ stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers.

Patterns of medication adherence and health care utilization among patients with chronic disease who were enrolled in a pharmacy assistance program.

BACKGROUND: Poor medication adherence due to high drug costs is a barrier to optimal health outcomes among low-income uninsured patients with chronic conditions. Charitable pharmacy assistance programs provide medications to such patients, but little is known about the utilization patterns of program participants. METHODS: We used a retrospective cohort design to investigate 6-month outcomes for participants in the University of North Carolina (UNC) Health Care Pharmacy Assistance Program (PAP) who received medications indicated for hypertension, diabetes, and/or hyperlipidemia from 2009 through 2011. Logistic regression was used to analyze predictors of medication adherence and to evaluate the association between adherence and use of emergency and inpatient care. RESULTS: The 3 study cohorts included 866 patients receiving antihypertensive agents, 265 patients receiving oral glucose-lowering agents, and 455 patients receiving statins. When assessed 6 months after program enrollment, 52%, 45%, and 38% of patients in these 3 groups, respectively, were at least 80% adherent to treatment. Adherent patients in all cohorts had lower odds of requiring inpatient or emergency department care, but the decrease was only statistically significant among those taking antihypertensive agents (odds ratio for hospitalization = 0.58; 95% confidence interval, 0.39-0.87). LIMITATIONS: Selection bias and inability to capture utilization data from sources other than UNC Health Care may have biased results. CONCLUSION: Approximately 50% of PAP participants were adherent to chronic disease medications. Adherence to such therapies among patients who are receiving financial assistance with medications may reduce their need for costly health care services. Future research should assess the long-term ability of pharmacy assistance programs to promote medication adherence and should examine alternative strategies for improving adherence and health outcomes among low-income uninsured patients.

The University of North Carolina's Health Care Pharmacy Assistance Progam.

BACKGROUND: UNC Health Care has a Pharmacy Assistance Program (PAP) that provides financial assistance to uninsured patients in North Carolina who need prescription medications. Despite significant investment in the program, little is known about the patients accessing it or the specific health care services they use. Our objectives were to describe the PAP population, to examine their use of prescription medications and health services, and to characterize changes in prescription medication use and expenditures from 2009 through 2011. METHODS: We used a repeated cross-sectional study design, merging prescription claims with health records from Carolina Data Warehouse for Health, to measure use of prescription medications and use of inpatient, outpatient, and emergency department care by PAP participants. Prescription claims were grouped into therapeutic categories. We generated descriptive statistics for key variables to examine health service utilization from 2009 through 2011. RESULTS: From 2009 through 2011, PAP served 7,180 patients from 81 counties in North Carolina. PAP users received a mean of 23 prescriptions, at an average cost of $754 per recipient per year. An average of $2.93 million per year was spent on the program, with an 8% rise in spending from 2009 to 2011. Inpatient care and emergency department care were utilized by 30% and 31% of PAP users, respectively, and there was minimal change in these rates over 3 years. LIMITATIONS: Data were limited to medications dispensed through PAP and to health services provided by UNC Health Care. CONCLUSIONS: With the state's decision to not expand Medicaid, PAP will continue to be an important resource for North Carolina's low income citizens.

A renaissance in pharmacy education at the University of North Carolina at Chapel Hill.

The UNC Eshelman School of Pharmacy is transforming its doctor of pharmacy program to emphasize active engagement of students in the classroom, foster scientific inquiry and innovation, and immerse students in patient care early in their education. The admissions process is also being reengineered.

Drosophila Models Uncover Substrate Channeling Effects on Phospholipids and Sphingolipids in Peroxisomal Biogenesis Disorders.

Peroxisomal Biogenesis Disorders Zellweger Spectrum (PBD-ZSD) disorders are a group of autosomal recessive defects in peroxisome formation that produce a multi-systemic disease presenting at birth or in childhood. Well documented clinical biomarkers such as elevated very long chain fatty acids (VLCFA) are key biochemical diagnostic findings in these conditions. Additional, secondary biochemical alterations such as elevated very long chain lysophosphatidylcholines are allowing newborn screening for peroxisomal disease. In addition, a more widespread impact on metabolism and lipids is increasingly being documented by metabolomic and lipidomic studies. Here we utilize Drosophila models of pex2 and pex16 as well as human plasma from individuals with PEX1 mutations. We identify phospholipid abnormalities in Drosophila larvae and brain characterized by differences in the quantities of phosphatidylcholine (PC) and phosphatidylethanolamines (PE) with long chain lengths and reduced levels of intermediate chain lengths. For diacylglycerol (DAG) the precursor of PE and PC through the Kennedy pathway, the intermediate chain lengths are increased suggesting an imbalance between DAGs and PE and PC that suggests the two acyl chain pools are not in equilibrium. Altered acyl chain lengths are also observed in PE ceramides in the fly models. Interestingly, plasma from human subjects exhibit phospholipid alterations similar to the fly model. Moreover, human plasma shows reduced levels of sphingomyelin with 18 and 22 carbon lengths but normal levels of C24. Our results suggest that peroxisomal biogenesis defects alter shuttling of the acyl chains of multiple phospholipid and ceramide lipid classes, whereas DAG species with intermediate fatty acids are more abundant. These data suggest an imbalance between de novo synthesis of PC and PE through the Kennedy pathway and remodeling of existing PC and PE through the Lands cycle. This imbalance is likely due to overabundance of very long and long acyl chains in PBD and a subsequent imbalance due to substrate channeling effects. Given the fundamental role of phospholipid and sphingolipids in nervous system functions, these observations suggest PBD-ZSD are diseases characterized by widespread cell membrane lipid abnormalities.