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1.  Introduction: A welcome to the first special animal health issue of AAPS PharmSci 
AAPS PharmSci  2002;4(4):189-192.
The goal of this special volume is to provide veterinary scientists with state-of-the art reviews in animal health and to inform human health scientists of the various challenges and collaborative opportunities associated with their animal health counterparts. The contributors are highly respected experts, providing invaluable insights into current issues and state-of-the-art advances within veterinary medicine.
doi:10.1208/ps040439
PMCID: PMC2751328  PMID: 12647740
Veterinary medicine; harmonization
2.  Role for the A Domain of Unprocessed Accumulation-Associated Protein (Aap) in the Attachment Phase of the Staphylococcus epidermidis Biofilm Phenotype 
Journal of Bacteriology  2014;196(24):4268-4275.
The polysaccharide intercellular adhesin or the cell wall-anchored accumulation-associated protein (Aap) mediates cellular accumulation during Staphylococcus epidermidis biofilm maturation. Mutation of sortase, which anchors up to 11 proteins (including Aap) to the cell wall, blocked biofilm development by the cerebrospinal fluid isolate CSF41498. Aap was implicated in this phenotype when Western blots and two-dimensional (2D) electrophoresis revealed increased levels of the protein in culture supernatants. Unexpectedly, reduced levels of primary attachment were associated with impaired biofilm formation by CSF41498 srtA and aap mutants. In contrast to previous studies, which implicated Aap proteolytic cleavage and, specifically, the Aap B domains in biofilm accumulation, the CSF41498 Aap protein was unprocessed. Furthermore, aap appeared to play a less important role in the biofilm phenotype of S. epidermidis 1457, in which the Aap protein is processed. Anti-Aap A-domain IgG inhibited primary attachment and biofilm formation in strain CSF41498 but not in strain 1457. The nucleotide sequences of the aap gene A-domain region and cleavage site in strains CSF41498 and 1457 were identical, implicating altered protease activity in the differential Aap processing results in the two strains. These data reveal a new role for the A domain of unprocessed Aap in the attachment phase of biofilm formation and suggest that extracellular protease activity can influence whether Aap contributes to the attachment or accumulation phases of the S. epidermidis biofilm phenotype.
doi:10.1128/JB.01946-14
PMCID: PMC4248850  PMID: 25266380
3.  Korean Medication Algorithm Project for Bipolar Disorder: third revision 
Objective
To constitute the third revision of the guidelines for the treatment of bipolar disorder issued by the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP 2014).
Methods
A 56-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for the various phases of bipolar disorder and for special populations. The review committee included 110 Korean psychiatrists and 38 experts for child and adolescent psychiatry. Of the committee members, 64 general psychiatrists and 23 child and adolescent psychiatrists responded to the survey.
Results
The treatment of choice (TOC) for euphoric, mixed, and psychotic mania was the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP); the TOC for acute mild depression was monotherapy with MS or AAP; and the TOC for moderate or severe depression was MS plus AAP/antidepressant. The first-line maintenance treatment following mania or depression was MS monotherapy or MS plus AAP; the first-line treatment after mania was AAP monotherapy; and the first-line treatment after depression was lamotrigine (LTG) monotherapy, LTG plus MS/AAP, or MS plus AAP plus LTG. The first-line treatment strategy for mania in children and adolescents was MS plus AAP or AAP monotherapy. For geriatric bipolar patients, the TOC for mania was AAP/MS monotherapy, and the TOC for depression was AAP plus MS or AAP monotherapy.
Conclusion
The expert consensus in the KMAP-BP 2014 differed from that in previous publications; most notably, the preference for AAP was increased in the treatment of acute mania, depression, and maintenance treatment. There was increased expert preference for the use of AAP and LTG. The major limitation of the present study is that it was based on the consensus of Korean experts rather than on experimental evidence.
doi:10.2147/NDT.S77838
PMCID: PMC4348143  PMID: 25750530
pharmacological treatment; treatment guideline; expert consensus
4.  Relative Precision of Inhaler Aerodynamic Particle Size Distribution (APSD) Metrics by Full Resolution and Abbreviated Andersen Cascade Impactors (ACIs): Part 1 
AAPS PharmSciTech  2010;11(2):843-851.
The purpose of this study was to compare relative precision of two different abbreviated impactor measurement (AIM) systems and a traditional multi-stage cascade impactor (CI). The experimental design was chosen to provide separate estimates of variability for each impactor type. Full-resolution CIs are useful for characterizing the aerosol aerodynamic particle size distribution of orally inhaled products during development but are too cumbersome, time-consuming, and resource-intensive for other applications, such as routine quality control (QC). This article presents a proof-of-concept experiment, where two AIM systems configured to provide metrics pertinent to QC (QC-system) and human respiratory tract (HRT-system) were evaluated using a hydrofluoroalkane-albuterol pressurized metered dose inhaler. The Andersen eight-stage CI (ACI) served as the benchmark apparatus. The statistical design allowed estimation of precision with each CI configuration. Apart from one source of systematic error affecting extra-fine particle fraction from the HRT-system, no other bias was detected with either abbreviated system. The observed bias was shown to be caused by particle bounce following the displacement of surfactant by the shear force of the airflow diverging above the collection plate of the second impaction stage. A procedure was subsequently developed that eliminated this source of error, as described in the second article of this series (submitted to AAPS PharmSciTech). Measurements obtained with both abbreviated impactors were very similar in precision to the ACI for all measures of in vitro performance evaluated. Such abbreviated impactors can therefore be substituted for the ACI in certain situations, such as inhaler QC or add-on device testing.
doi:10.1208/s12249-010-9452-6
PMCID: PMC2902354  PMID: 20480271
AIM; APSD; impactor; inhaler; simplified
5.  Use of on-demand video to provide patient education on spinal cord injury 
Background/objective
Persons with chronic spinal cord injury (SCI) have a high lifetime need for ongoing patient education to reduce the risk of serious and costly medical conditions. We have addressed this need through monthly in-person public education programs called SCI Forums. More recently, we began videotaping these programs for streaming on our website to reach a geographically diverse audience of patients, caregivers, and providers.
Design/methods
We compared information from the in-person forums to that of the same forums shown streaming on our website during a 1-year period.
Results
Both the in-person and Internet versions of the forums received high overall ratings from individuals who completed evaluation forms. Eighty-eight percent of online evaluators and 96% of in-person evaluators reported that they gained new information from the forum; 52 and 64% said they changed their attitude, and 61 and 68% said they would probably change their behavior or take some kind of action based on information they learned. Ninety-one percent of online evaluators reported that video is better than text for presenting this kind of information.
Conclusion
Online video is an accessible, effective, and well-accepted way to present ongoing SCI education and can reach a wider geographical audience than in-person presentations.
doi:10.1179/2045772311Y.0000000015
PMCID: PMC3152812  PMID: 21903014
Patient education; Spinal cord injuries; Media; Print; Digital; Video; Internet; Secondary complications; Prevention; Self-care; Quality of life
6.  2012 AAPS National Biotech Conference Open Forum: A Perspective on the Current State of Immunogenicity Prediction and Risk Management 
The AAPS Journal  2013;15(4):1155-1159.
The immunogenicity profile of a biotherapeutic is determined by multiple product-, process- or manufacturing-, patient- and treatment-related factors and the bioanalytical methodology used to monitor for immunogenicity. This creates a complex situation that limits direct correlation of individual factors to observed immunogenicity rates. Therefore, mechanistic understanding of how these factors individually or in concert could influence the overall incidence and clinical risk of immunogenicity is crucial to provide the best benefit/risk profile for a given biotherapeutic in a given indication and to inform risk mitigation strategies. Advances in the field of immunogenicity have included development of best practices for monitoring anti-drug antibody development, categorization of risk factors contributing to immunogenicity, development of predictive tools, and development of effective strategies for risk management and mitigation. Thus, the opportunity to ask "where we are now and where we would like to go from here?" was the main driver for organizing an Open Forum on Improving Immunogenicity Risk Prediction and Management, conducted at the 2012 American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference in San Diego. The main objectives of the Forum include the following: to understand the nature of immunogenicity risk factors, to identify analytical tools used and animal models and management strategies needed to improve their predictive value, and finally to identify collaboration opportunities to improve the reliability of risk prediction, mitigation, and management. This meeting report provides the Forum participant's and author's perspectives on the barriers to advancing this field and recommendations for overcoming these barriers through collaborative efforts.
doi:10.1208/s12248-013-9520-4
PMCID: PMC3787208  PMID: 23990501
ADA; anti-drug antibodies; immunogenicity; neutralizing antibodies; prediction; predictive sciences; risk assesment; risk management; risk mitigation
7.  eGEMs’ Early Adventures in Open Access Publishing 
eGEMs  2014;2(1):1157.
Introduction:
In January 2013 AcademyHealth officially launched eGEMs (Generating Evidence and Methods to improve patient outcomes) to rapidly disseminate peer-reviewed approaches using electronic health data (EHD) to advance research and quality improvement (QI), with the overall goal of improving patient and community outcomes. Inspired by the publication of eGEMs 50th paper, Dr. Erin Holve, eGEMs editor-in-chief reviews the EDM Forum’s early experiences with open access publishing.
eGEMs to Date:
As of the end of September 2014 eGEMs has published 59 manuscripts and received nearly 150 submissions. These early findings demonstrate eGEMs is filling a need for dissemination outlets that bridge the gap between the health research and practice communities. Published papers are distributed across the EDM Forum’s four thematic domains: governance (n=5), informatics (n=14), methods (n=13) and learning health systems (n=27). While system design issues are a consistent theme, papers addressing priority health topics such as diabetes, asthma, and obesity are frequently submitted. Authors include more than two hundred experts in the field representing nearly all of the EDM Forum’s core stakeholder groups: research/QI, nonprofit/policy, healthcare delivery, government, industry, and patients/consumers.
What’s Next:
With the help of our diverse community, eGEMs will continue to expand its depth and reach. Forthcoming special issues on community-level transformation using health IT, and ways to improve user-experience and system design will add to the journal’s robust portfolio of work identifying and addressing shared challenges using EHD. The EDM Forum, working closely with our partners at the Agency for Healthcare Research and Quality, will work diligently to ensure eGEMs is accelerating the pace at which the community translates and disseminates key lessons, with the ultimate goal of helping transform knowledge into actions that can improve health and health care.
doi:10.13063/2327-9214.1157
PMCID: PMC4371423  PMID: 25848602
learning health system; comparative effectiveness research; patient-centered outcomes research; quality improvement; eGEMs quarterly editorial
8.  Axenic Leishmania amazonensis Promastigotes Sense both the External and Internal Arginine Pool Distinctly Regulating the Two Transporter-Coding Genes 
PLoS ONE  2011;6(11):e27818.
Leishmania (L.) amazonensis uses arginine to synthesize polyamines to support its growth and survival. Here we describe the presence of two gene copies, arranged in tandem, that code for the arginine transporter. Both copies show similar Open Reading Frames (ORFs), which are 93% similar to the L. (L.) donovani AAP3 gene, but their 5′ and 3′ UTR's have distinct regions. According to quantitative RT-PCR, the 5.1 AAP3 mRNA amount was increased more than 3 times that of the 4.7 AAP3 mRNA along the promastigote growth curve. Nutrient deprivation for 4 hours and then supplemented or not with arginine (400 µM) resulted in similar 4.7 AAP3 mRNA copy-numbers compared to the starved and control parasites. Conversely, the 5.1 AAP3 mRNA copy-numbers increased in the starved parasites but not in ones supplemented with arginine (p<0.05). These results correlate with increases in amino acid uptake. Both Meta1 and arginase mRNAs remained constant with or without supplementation. The same starvation experiment was performed using a L. (L.) amazonensis null knockout for arginase (arg-) and two other mutants containing the arginase ORF with (arg-/ARG) or without the glycosomal addressing signal (arg-/argΔSKL). The arg- and the arg-/argΔSKL mutants did not show the same behavior as the wild-type (WT) parasite or the arg-/ARG mutant. This can be an indicative that the internal pool of arginine is also important for controlling transporter expression and function. By inhibiting mRNA transcription or/and mRNA maturation, we showed that the 5.1 AAP3 mRNA did not decay after 180 min, but the 4.7 AAP3 mRNA presented a half-life decay of 32.6 +/− 5.0 min. In conclusion, parasites can regulate amino acid uptake by increasing the amount of transporter-coding mRNA, possibly by regulating the mRNA half-life in an environment where the amino acid is not present or is in low amounts.
doi:10.1371/journal.pone.0027818
PMCID: PMC3218042  PMID: 22114701
9.  AlzPharm: integration of neurodegeneration data using RDF 
BMC Bioinformatics  2007;8(Suppl 3):S4.
Background
Neuroscientists often need to access a wide range of data sets distributed over the Internet. These data sets, however, are typically neither integrated nor interoperable, resulting in a barrier to answering complex neuroscience research questions. Domain ontologies can enable the querying heterogeneous data sets, but they are not sufficient for neuroscience since the data of interest commonly span multiple research domains. To this end, e-Neuroscience seeks to provide an integrated platform for neuroscientists to discover new knowledge through seamless integration of the very diverse types of neuroscience data. Here we present a Semantic Web approach to building this e-Neuroscience framework by using the Resource Description Framework (RDF) and its vocabulary description language, RDF Schema (RDFS), as a standard data model to facilitate both representation and integration of the data.
Results
We have constructed a pilot ontology for BrainPharm (a subset of SenseLab) using RDFS and then converted a subset of the BrainPharm data into RDF according to the ontological structure. We have also integrated the converted BrainPharm data with existing RDF hypothesis and publication data from a pilot version of SWAN (Semantic Web Applications in Neuromedicine). Our implementation uses the RDF Data Model in Oracle Database 10g release 2 for data integration, query, and inference, while our Web interface allows users to query the data and retrieve the results in a convenient fashion.
Conclusion
Accessing and integrating biomedical data which cuts across multiple disciplines will be increasingly indispensable and beneficial to neuroscience researchers. The Semantic Web approach we undertook has demonstrated a promising way to semantically integrate data sets created independently. It also shows how advanced queries and inferences can be performed over the integrated data, which are hard to achieve using traditional data integration approaches. Our pilot results suggest that our Semantic Web approach is suitable for realizing e-Neuroscience and generic enough to be applied in other biomedical fields.
doi:10.1186/1471-2105-8-S3-S4
PMCID: PMC1892101  PMID: 17493287
10.  AAPS/RAPS/CAPRA collaborative program: Exploring the challenges of drug regulation in a global environment: Clinical concerns 
AAPS PharmSci  2003;5(4):13-40.
Globalization of the pharmaceutical industry has led to a need to harmonize the regulatory requirements governing the marketing of medicinal products. To minimize the barriers impeding global drug product registration, the International Conference on the Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH) was established in 1990. The ICH has developed a series of guidelines that reflect agreements reached by participating nations on aspects of the chemistry and clinical technical sections that will fulfill the regulatory requirements of these various jurisdications. Nevertheless, there continue to be points of divergent perspectives and barriers that can impede the use of foreign clinical data. Given the importance of these issues, the Regulatory Science (RS) section of the American Association of Pharmaceutical Scientists (AAPS), in conjunction with the Regulatory Affairs Professional Society (RAPS) and the Canadian Association of Professional Regulatory Affairs (CAPRA) cosponsored a public forum on this topic. This manuscript provides a summary of the speaker presentations and audience discussions regarding the design of clinical trials and the extrapolation of results from these trials to support international drug registration.
doi:10.1208/ps050427
PMCID: PMC2750989  PMID: 15198515
clinical trials; regulatory requirements; international harmonization; foreign clinical data
11.  Identification and Characterization of Nuclear and Nucleolar Localization Signals in the Adeno-Associated Virus Serotype 2 Assembly-Activating Protein 
Journal of Virology  2014;89(6):3038-3048.
ABSTRACT
Assembly-activating protein (AAP) of adeno-associated virus serotype 2 (AAV2) is a nucleolar-localizing protein that plays a critical role in transporting the viral capsid VP3 protein to the nucleolus for assembly. Here, we identify and characterize AAV2 AAP (AAP2) nuclear (NLS) and nucleolar (NoLS) localization signals near the carboxy-terminal region of AAP2 (amino acid positions 144 to 184) (AAP2144–184). This region contains five basic-amino-acid-rich (BR) clusters, KSKRSRR (AAP2BR1), RRR (AAP2BR2), RFR (AAP2BR3), RSTSSR (AAP2BR4), and RRIK (AAP2BR5), from the amino terminus to the carboxy terminus. We created 30 AAP2BR mutants by arginine/lysine-to-alanine mutagenesis or deletion of AAP2BRs and 8 and 1 green fluorescent protein (GFP)-AAP2BR and β-galactosidase–AAP2BR fusion proteins, respectively, and analyzed their intracellular localization in HeLa cells by immunofluorescence microscopy. The results showed that AAP2144–184 has redundant multipartite NLSs and that any combinations of 4 AAP2BRs, but not 3 or less, can constitute a functional NLS-NoLS; AAP2BR1 and AAP2BR2 play the most influential role for nuclear localization, but either one of the two AAP2BRs is dispensable if all 4 of the other AAP2BRs are present, resulting in 3 different, overlapping NLS motifs; and the NoLS is shared redundantly among the five AAP2BRs and functions in a context-dependent manner. AAP2BR mutations not only resulted in aberrant intracellular localization, but also attenuated AAP2 protein expression to various degrees, and both of these abnormalities have a significant negative impact on capsid production. Thus, this study reveals the organization of the intermingling NLSs and NoLSs in AAP2 and provides insights into their functional roles in capsid assembly.
IMPORTANCE Adeno-associated virus (AAV) has become a popular and successful vector for in vivo gene therapy; however, its biology has yet to be fully understood. In this regard, the recent discovery of the assembly-activating protein (AAP), a nonstructural, nucleolar-localizing AAV protein essential for viral capsid assembly, has provided us a new opportunity to better understand the fundamental processes required for virion formation. Here, we identify clusters of basic amino acids in the carboxy terminus of AAP from AAV serotype 2 (AAV2) that act as nuclear and nucleolar localization signals. We also demonstrate their importance in maintaining AAP expression levels and efficient production of viral capsids. Insights into the functions of AAP can elucidate the requirements and process for AAV capsid assembly, which may lead to improved vector production for use in gene therapy. This study also contributes to the growing body of work on nuclear and nucleolar localization signals.
doi:10.1128/JVI.03125-14
PMCID: PMC4337552  PMID: 25552709
12.  Scholarly Contributions of Required Senior Research Projects in a Doctor of Pharmacy Curriculum 
Objective. To determine dissemination outcomes and faculty perceptions of senior research projects conducted from 2008 to 2011 by PharmD students in a curricular pathway focused on direct patient care.
Methods. Preceptors’ reported dissemination outcomes of research projects were surveyed and their perceptions of the precepting experience were rated using a web-based survey. Results were compared to those from an earlier pharmaceutical care cohort (2002-2007) and a combined cohort of 2, more research-intensive curricular pathways at the school.
Results. The overall response rate was 90.2%. Project dissemination included 61.3% at an institutional forum, 42.3% as a submitted publication, 37.8% as a poster, and 4.5% as an oral presentation. Projects completed from 2008-2011 were significantly more likely than those from 2002-2007 to be submitted for publication (42.3% vs 10.7%, p<0.001) and published (28.8% vs 5.3%, p<0.001). Most preceptors found their research projects valuable to them professionally (88.3%) and to their own or another institution (83.5% and 78.5%, respectively). Ninety-five percent of preceptors would precept again.
Conclusion. Dissemination rates for pharmaceutical care projects increased over time. Despite modest dissemination levels, the majority of preceptors agreed that required student research projects provide a valuable learning experience for students.
doi:10.5688/ajpe79223
PMCID: PMC4386744  PMID: 25861104
student; research; education; curriculum; scholarship; information dissemination
13.  Dual Degree Programs at the University of Kentucky College of Pharmacy 
The rapid growth and evolution of the pharmacy profession has created a wide array of opportunities for graduating pharmacists beyond traditional community pharmacy or hospital practice. Management and leadership positions in federal and state healthcare agencies, pharmaceutical companies, hospitals, retail pharmacies, academia and managed care organizations increasingly require the pharmaceutical knowledge obtained through a doctor of pharmacy (PharmD) degree combined with financial, organizational, and management skills. In these innovative positions, pharmacists are being called upon to assume responsibilities as executives and administrators in systems providing pharmacist care services to patients.
To endow students with knowledge and skills required to perform the duties required in these decision-making positions, the University of Kentucky College of Pharmacy has established 3 joint degree programs: the PharmD/Master of Business Administration (PharmD/MBA), PharmD/Master of Public Administration (PharmD/MPA), and PharmD/Master of Science in Economics (PharmD/MS). This paper describes these joint degree programs.
PMCID: PMC2254237  PMID: 18322574
dual degree; joint degree; education; doctor of pharmacy degree; master of business administration; master of public administration
14.  Evaluation of a Required Senior Research Project in a Doctor of Pharmacy Curriculum 
Objective
To characterize the dissemination of study findings and assess project preceptor attitudes towards a required senior research project in a doctor of pharmacy (PharmD) curriculum.
Methods
A survey was conducted to determine preceptors' perceptions of the value of a required pharmacy student research project and dissemination of research results.
Results
One hundred fifteen project preceptors (92.0%) responded. Most preceptors agreed that the projects provided a valuable learning experience to the students (87.5%) and were of value to them professionally (82.1%) and to their institution (78.2%). Study findings were disseminated primarily through institutional forums (47.3%). A smaller percentage of projects were disseminated externally through presentations at professional meetings (23.7%, poster presentations; 4.0%, platform presentations), and peer-reviewed publications (5.3%).
Conclusions
Despite a modest level of dissemination of project results through presentations at professional meetings and a low level of dissemination via published manuscripts, the majority of preceptors perceived a required student research project to be of value.
PMCID: PMC3049664  PMID: 21451757
doctor of pharmacy degree; research; student research; curriculum requirements
15.  Unnecessary Child Care Exclusions in a State That Endorses National Exclusion Guidelines 
Pediatrics  2010;125(5):1003-1009.
OBJECTIVE
No study has evaluated the association between state endorsement of American Academy of Pediatrics (AAP) and American Public Health Association (APHA) national guidelines and unnecessary exclusion decisions. We sought to determine the rate of unnecessary exclusion decisions by child care directors in a state that endorses AAP/APHA guidelines and to identify factors that are associated with higher unnecessary exclusion decisions.
METHODS
A telephone survey was administered to directors in metropolitan Milwaukee, Wisconsin. Directors were randomly sampled from a list of 971 registered centers. Director, center, and neighborhood characteristics were obtained. Directors reported whether immediate exclusion was indicated for 5 vignettes that featured children with mild illness that do not require exclusion by AAP/APHA guidelines. Weighted data were summarized by using descriptive statistics. Regression analysis was used to identify factors that were associated with directors’ exclusion decisions.
RESULTS
A total of 305 directors completed the survey. Overall, directors would unnecessarily exclude 57% of children. More than 62% had never heard of the AAP/APHA guidelines. Regression analysis showed fewer exclusions among more experienced compared with less experienced directors, among larger centers compared with smaller centers, and among centers that were located in areas with a higher percentage of female heads of household. Centers with ≤10% children on state-assisted tuition excluded more.
CONCLUSIONS
High rates of inappropriate exclusion persist despite state endorsement of AAP/APHA guidelines. Focused initial and ongoing training of directors regarding AAP/APHA guidelines may help to reduce high rates of unnecessary exclusions.
doi:10.1542/peds.2009-2283
PMCID: PMC3047469  PMID: 20403929
child care; exclusion; mild illness
16.  Detection of the Metabolic Syndrome in Schizophrenia and Implications for Antipsychotic Therapy: Is There a Role for Folate? 
Molecular diagnosis & therapy  2013;17(1):21-30.
In general, presence of the metabolic syndrome is associated with significant cardiovascular mortality and represents a growing public health concern in the United States. Patients with a schizophrenia have a three times greater risk of death compared to the general population, with cardiovascular disease being the most common cause of this mortality. Use of the atypical antipsychotics (AAPs) to treat schizophrenia contributes significantly to this cardiovascular disease risk. While currently several different clinical guidelines exist to monitor for the metabolic consequences of AAP use, implementation is lacking. Due to the under monitoring of side effects and the lack of alternative treatment choices in schizophrenia, research has focused on the identification of various biomarkers and pharmacogenomic targets to focus on those at greatest risk for metabolic syndrome, thus aiming to increase the efficacy and minimize the side effects of the AAPs. This has led to several different lines of research. This manuscript focuses on summarizing the differing metabolic syndrome criteria, monitoring guidelines for AAPs and the role of folic acid as it relates to metabolic syndrome within the schizophrenia population. It will concentrate not only on the pharmacogenomics of folic acid metabolism, but also its epigenetic interaction with the environment. From this work, genetic variation within both the methylenetetrahydrofolate reductase (MTHFR) and catechol-o-methyl transferase (COMT) genes has been associated with increased metabolic syndrome risk in schizophrenia patients treated with AAPs. Furthermore, the combination of folate pharmacogenetics and epigenetics has uncovered relationships between methylation, schizophrenia disease, treatment type and metabolic syndrome. Despite the several areas of biomarker research for schizophrenia related metabolic syndrome, translation to the clinical setting is still lacking and further studies are needed to bridge this gap. Future folate supplementation research may prove to be an easy and effective clinical tool for the prevention and/or treatment of metabolic syndrome associated with AAP treatment, but clearly more work needs to be done in this area.
doi:10.1007/s40291-013-0017-8
PMCID: PMC4077272  PMID: 23341251
Schizophrenia; Metabolic Syndrome; Folic Acid; Homocysteine; MTHFR; Epigenetics
17.  The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes 
The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM) on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC—in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE)—has great merits for skin regeneration. In this study, human primary keratinocytes (HKs), which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 μg/mL) than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05) notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 μg/mL). AAPE treatment significantly stimulated stress fiber formation, which was linked to the RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-β3 differing from that shown by 2-D analysis. Conclusion: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration.
doi:10.3390/ijms13011239
PMCID: PMC3269749  PMID: 22312315
ADSC-CM; AAPE; stress fiber formation; RhoA-ROCK signaling; regeneration; proliferation; migration
18.  Pharmacy students’ perspectives on a PharmD/MPH dual degree program at a large metropolitan school of pharmacy 
Pharmacy Practice  2014;12(1):359.
Objective
To determine doctor of pharmacy (PharmD) students’ perceptions of a PharmD and master of public health (MPH) dual degree program.
Methods
A seven-item survey instrument was developed and distributed to students at a large metropolitan school of pharmacy during scheduled class time in April 2012.
Results
Among the 611 students enrolled in the PharmD program, 447 (73%) responded. Of those who responded, 72.3% were either “very likely” or “likely” to consider enrolling in such a PharmD/MPH dual degree program, and 77.4% believed that it would be attractive to future students. The most commonly identified potential limitations to pursuing the dual degree were time commitment (19.9%), increased workload and stress (11.2%), and tuition cost (10.3%). The most notable advantages documented were increased job opportunities for public health-related pharmacy positions (26.9%), increased ability to serve patients and the community (13.4%), and increased marketability for future jobs (8.7%).
Conclusions
PharmD student participants demonstrated overall positive attitudes and interest towards a PharmD/MPH dual degree program.
PMCID: PMC3955862  PMID: 24644517
Education, Pharmacy; Students, Pharmacy; Students, Public Health; Schools, Pharmacy; Program Development; Attitude; United States
19.  Credentials for a PharmD graduate: The voyage never ends 
SAGE Open Medicine  2015;3:2050312115584228.
Doctor of Pharmacy (PharmD) is a professional pharmacy degree qualification offered by universities world-wide. While the graduates from the West are familiar with scope and job opportunities that present on completion of a PharmD degree, graduates from Asia and the Middle-East are coming to grips with the future of PharmD program and the role that it could play in career advancement. Through this review, we would like to highlight that numerous credential programs are available which can be added to the armory of PharmD graduates for advancement of their professional careers. The credentials detailed in this review are designed for PharmD graduates to optimize pharmaceutical care in specialized clinical settings such as geriatrics and ambulatory medicine. We have assembled an extensive list of post-PharmD educational opportunities to enhance professional practice for pharmacy graduates.
doi:10.1177/2050312115584228
PMCID: PMC4679279  PMID: 26770783
PharmD; doctor of pharmacy; credentials
20.  Does a transition in education equate to a transition in practice? Thai stakeholder’s perceptions of the introduction of the Doctor of Pharmacy programme 
BMC Medical Education  2015;15:205.
Background
Pharmacy education and pharmacy practice are facing remarkable changes following new scientific discoveries, evolving patient needs and the requirements of advanced pharmacy competency for practices. Many countries are introducing or undertaking major transformations in pharmacy education. The Thai pharmacy curriculum has been changed from a 5-year BPharm and a 6-year PharmD to only a 6-year PharmD programme. Curriculum change processes usually involve stakeholders, including both internal and external educational institutions, at all levels. This study aims to understand the experiences and perceptions of stakeholders regarding the transition to an all-PharmD programme in Thailand.
Methods
Semi-structured interviews were conducted in Thailand with 130 stakeholders (e.g., policy makers, pharmacy experts, educators, health care providers, patients, students and parents) from August-October 2013. The interviews were audio recorded, transcribed verbatim and analysed using an inductive thematic analysis.
Results
Three main themes were derived from the findings: 1. influences on curriculum change (e.g., the needs of pharmacists to provide better patient care, the US-Thai consortium for the development of pharmacy education); 2. perceived benefits (e.g., improve pharmacy competencies from generalists to specialists, ready to work after graduation, providing a high quality of patient care); and 3. concerns (e.g., the higher costs of study for a longer period of time, the mismatch between the pharmacy graduates’ competency and the job market’s needs, insufficient preceptors and training sites, lack of practical experience of the faculty members and issues related to the separate licenses that are necessary due to the difference in the graduates’ specialties).
Conclusions
This is the first study to highlight the issues surrounding the transition to the 6-year PharmD programme in Thailand, which was initiated due to the need for higher levels of competency among the nation’s pharmacists. The transition was influenced by many factors. Many participants perceived benefits from the new pharmacy curriculum. However, some participants were concerned about this transition. Although most of the respondents accepted the need to go forward to the 6-year PharmD programme, designing an effective curriculum, providing a sufficient number of qualified PharmD preceptors, determining certain competencies of pharmacists in different practices and monitoring the quality of pharmacy education still need to be addressed during this transitional stage of pharmacy education in Thailand.
doi:10.1186/s12909-015-0473-4
PMCID: PMC4653906  PMID: 26585968
Stakeholders; Perceptions; Transition; PharmD programme; Preceptors; Workforce; Thailand; A qualitative study
21.  Management of neonatal hyperbilirubinemia: Pediatricians' practices and educational needs 
BMC Pediatrics  2006;6:6.
Background
Early detection and treatment of neonatal hyperbilirubinemia is important in the prevention of bilirubin-induced encephalopathy. In this study, we evaluated the New Jersey pediatricians' practices and beliefs regarding the management of neonatal hyperbilirubinemia and their compliance with the recommendations made by the American Academy of Pediatrics (AAP) in 1994.
Methods
A survey questionnaire was mailed to a random sample of 800 pediatricians selected from a list of 1623 New Jersey Fellows of the AAP initially in October 2003 and then in February 2004 for the non-respondents. In addition to the physicians' demographic characteristics, the questionnaire addressed various aspects of neonatal hyperbilirubinemia management including the diagnosis, treatment, and follow up as well as the pediatricians' beliefs regarding the significance of risk factors in the development of severe hyperbilirubinemia.
Results
The adjusted response rate of 49.1% (n = 356) was calculated from the 725 eligible respondents. Overall, the practicing pediatricians reported high utilization (77.9%) of the cephalocaudal progression of jaundice and low utilization (16.1%) of transcutaneous bilirubinometry for the quantification of the severity of jaundice. Most of the respondents (87.4%) identified jaundice as an indicator for serum bilirubin (TSB) testing prior to the neonate's discharge from hospital, whereas post-discharge, only 57.7% felt that a TSB was indicated (P < 0.01). If the neonate's age was under 72 hours, less than one-third of the respondents reported initiation of phototherapy at TSB levels lower than the treatment parameters recommended by the AAP in 1994, whereas if the infant was more than 72 hours old, almost 60% were initiating phototherapy at TSB lower than the 1994 AAP guidelines. Most respondents did not regard neonatal jaundice noted after discharge and gestational ages 37–38 weeks as being significant in the development of severe hyperbilirubinemia. However, the majority did recognize the importance of jaundice presenting within the first 24 hours and Rh/ABO incompatibility.
Conclusion
The pediatricians' practices regarding the low utilization of laboratory diagnosis for the quantification of jaundice after discharge and underestimation of risk factors that contribute to the development of severe hyperbilirubinemia are associated with initiation of phototherapy at lower than AAP recommended treatment parameters and recognition of neonatal hyperbilirubinemia as an important public health concern.
doi:10.1186/1471-2431-6-6
PMCID: PMC1450287  PMID: 16519797
22.  Funding and Forums for ELSI Research: Who (or What) is Setting the Agenda? 
AJOB primary research  2012;3(3):51-60.
Background
Discussion of the influence of money on bioethics research seems particularly salient in the context of research on the ethical, legal and social implications (ELSI) of human genomics, as this research may be financially supported by the ELSI Research Program. Empirical evidence regarding the funding of ELSI research and where such research is disseminated, in relation to the specific topics of the research and methods used, can help to further discussions regarding the appropriate influence of specific institutions and institutional contexts on ELSI and other bioethics research agendas.
Methods
We reviewed 642 ELSI publications (appearing between 2003–2008) for reported sources of funding, forum for dissemination, empirical and non-empirical methods, and topic of investigation.
Results
Most ELSI research is independent of direct grant-based funding sources; 66% reported no such sources of funding. The National Human Genome Research Institute (NHGRI) is the most dominant source of funding; 16% of publications acknowledged at least one source of NHGRI grant funding. Funding is acknowledged more frequently in empirical than non-empirical publications, and more frequently in publications in public health journals than in any other ELSI research dissemination forums. Dominant research topics vary by publication forum and by reported funding.
Conclusions
ELSI research is surprisingly independent of direct grant-based funding, yet correlations are apparent between this type of funding and publication placement, topics addressed, and methods used, implying a not insignificant influence on ELSI research agenda-setting. However, given the relatively low percentage of publications acknowledging external grant-based funding, as well as other significant correlations between publication placement and topics addressed, additional institutional contexts, perhaps related to professional advancement or valuation, may shape research agendas in ways that potentially exceed the direct influences of grant-based funding in this area. In some cases, grant-based funding may actually counter other potentially problematic institutional influences.
doi:10.1080/21507716.2012.678550
PMCID: PMC3413296  PMID: 22888470
Genomics [Ethics]; National Human Genome Research Institute (U.S.); Ethics, Professional
23.  A Pharmacotherapy Capstone Course to Advance Pharmacy Students’ Clinical Documentation Skills 
Objective. To implement and assess the effectiveness of a capstone pharmacotherapy course designed to integrate in-class curriculum using patient cases and drug-information questions. The course was intended to improve third-year doctor of pharmacy (PharmD) students' clinical documentation skills in preparation for beginning advanced pharmacy practice experiences (APPEs).
Design. This 2-credit, semester-long course consisted of 6 patient cases and 12 drug-information questions posted electronically on an Internet-based medical chart, a public health presentation, a knowledge examination, and an objective standardized performance assessment. In class, students engaged in active-learning exercises and clinical problem-solving. Students worked outside of class in small groups to retrieve and discuss assigned articles and review medication information in preparation for in-class discussions.
Assessment. A rubric was used to assess the patient cases and questions that students completed and submitted individually. Data for 4 consecutive course offerings (n=622) were then analyzed. A significant improvement was found in the “misplaced” but not the “missing” documentation ratings for both assessment and plan notes in the final assessment compared with baseline. In course evaluations, the majority of students agreed that the course integrated material across the curriculum (97%) and improved their clinical writing skills (80.5%).
Conclusion. A capstone pharmacy course was successful in integrating and reviewing much of the material covered across the PharmD curriculum and in improving students’ clinical documentation skills.
doi:10.5688/ajpe767134
PMCID: PMC3448472  PMID: 23049106
clinical documentation; clinical thinking; case-based learning; pharmacotherapy
24.  PathVisio 3: An Extendable Pathway Analysis Toolbox 
PLoS Computational Biology  2015;11(2):e1004085.
PathVisio is a commonly used pathway editor, visualization and analysis software. Biological pathways have been used by biologists for many years to describe the detailed steps in biological processes. Those powerful, visual representations help researchers to better understand, share and discuss knowledge. Since the first publication of PathVisio in 2008, the original paper was cited more than 170 times and PathVisio was used in many different biological studies. As an online editor PathVisio is also integrated in the community curated pathway database WikiPathways.
Here we present the third version of PathVisio with the newest additions and improvements of the application. The core features of PathVisio are pathway drawing, advanced data visualization and pathway statistics. Additionally, PathVisio 3 introduces a new powerful extension systems that allows other developers to contribute additional functionality in form of plugins without changing the core application.
PathVisio can be downloaded from http://www.pathvisio.org and in 2014 PathVisio 3 has been downloaded over 5,500 times. There are already more than 15 plugins available in the central plugin repository. PathVisio is a freely available, open-source tool published under the Apache 2.0 license (http://www.apache.org/licenses/LICENSE-2.0). It is implemented in Java and thus runs on all major operating systems. The code repository is available at http://svn.bigcat.unimaas.nl/pathvisio. The support mailing list for users is available on https://groups.google.com/forum/#!forum/wikipathways-discuss and for developers on https://groups.google.com/forum/#!forum/wikipathways-devel.
doi:10.1371/journal.pcbi.1004085
PMCID: PMC4338111  PMID: 25706687
25.  Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging 
Journal of Pharmaceutical Sciences  2015;104(5):1658-1667.
Tablet dissolution is strongly affected by swelling and solvent penetration into its matrix. A terahertz-pulsed imaging (TPI) technique, in reflection mode, is introduced as a new tool to measure one-dimensional swelling and solvent ingress in flat-faced pharmaceutical compacts exposed to dissolution medium from one face of the tablet. The technique was demonstrated on three tableting excipients: hydroxypropylmethyl cellulose (HPMC), Eudragit RSPO, and lactose. Upon contact with water, HPMC initially shrinks to up to 13% of its original thickness before undergoing expansion. HPMC and lactose were shown to expand to up to 20% and 47% of their original size in 24 h and 13 min, respectively, whereas Eudragit does not undergo dimensional change. The TPI technique was used to measure the ingress of water into HPMC tablets over a period of 24 h and it was observed that water penetrates into the tablet by anomalous diffusion. X-ray microtomography was used to measure tablet porosity alongside helium pycnometry and was linked to the results obtained by TPI. Our results highlight a new application area of TPI in the pharmaceutical sciences that could be of interest in the development and quality testing of advanced drug delivery systems as well as immediate release formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1658–1667, 2015
doi:10.1002/jps.24376
PMCID: PMC4415463  PMID: 25645509
terahertz pulsed imaging; diffusion; porosity; swelling; solid dosage forms; imaging methods; hydration; oral drug delivery; microstructure; X-ray micro computed tomography

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