Publications by authors named "Michelle King"

98 Publications

Patients Desire Personalized, Specific, and Continuous Advice on Weight Management.

South Med J 2021 Jan;114(1):41-45

From the Center for Value-Based Care Research and the Department of Family Medicine, Cleveland Clinic Community Care, the Strategy Office, Cleveland Clinic, and the Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio.

Objective: To deliver effective care, healthcare systems should understand patients' preferences for weight management across a spectrum of needs. Our objective was to describe patients' perceptions of what helps or hinders weight loss and maintenance.

Methods: Semistructured interviews were conducted with patients who accessed weight management services at a large integrated health system in 2018. The interview guide was developed and iteratively refined through a literature search and by consulting experts. Questions included the respondent's weight history, interactions with the health system, and current health status. The analysis used a grounded theory approach, and each transcript was double-coded in 2019. Codes were sorted into themes. All discrepancies were resolved through team discussion.

Results: Fifteen patients were interviewed. The majority of respondents (87%) reported multiple weight loss attempts. Three themes were identified. First, advice should be matched to a patient's knowledge and prior experience (eg, using bariatric deck cards). As patients progressed, clinician advice also needed to advance (eg, explaining how to expand food options instead of defining a healthy diet). Second, respondents had a variety of motivating factors, and understanding where motivation is generated from can inform how to design a weight management approach. Third, patients need continual and long-term advice. Some respondents feared becoming ineligible for services if their weight dropped too much.

Conclusions: Health systems can support patients by developing processes for identifying the extent of a patient's knowledge and giving personalized advice based on the patient's preferences and experiences. Reassessing needs at defined intervals may help patients attain and sustain their goals.
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http://dx.doi.org/10.14423/SMJ.0000000000001196DOI Listing
January 2021

, encoding a Ca-regulated putative phytase, is evolutionarily conserved in and has potential as a biomarker.

Microbiology (Reading) 2021 Feb;167(2)

Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK 74078, USA.

infects patients with cystic fibrosis, burns, wounds and implants. Previously, our group showed that elevated Ca positively regulates the production of several virulence factors in , such as biofilm formation, production of pyocyanin and secreted proteases. We have identified a Ca-regulated β-propeller putative phytase, CarP, which is required for Ca tolerance, regulation of the intracellular Ca levels, and plays a role in Ca regulation of virulence. Here, we studied the conservation of sequence and its occurrence in diverse phylogenetic groups of bacteria. analysis revealed that and its two paralogues PA2017 and PA0319 are primarily present in and belong to the core genome of the species. We identified 155 single nucleotide alterations within , 42 of which lead to missense mutations with only three that affected the predicted 3D structure of the protein. PCR analyses with -specific primers detected specifically in 70 clinical and environmental samples. Sequence comparison demonstrated that is overall highly conserved in isolated from diverse environments. Such evolutionary preservation of illustrates its importance for adaptations to diverse environments and demonstrates its potential as a biomarker.
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http://dx.doi.org/10.1099/mic.0.001004DOI Listing
February 2021

"If I were to do this, how would I experience it?" Developing a theoretical framework for exploring pharmacists' practice in the domain of assisted dying.

Res Social Adm Pharm 2020 Jun 2:685-693. Epub 2020 Jun 2.

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Canada. Electronic address:

Background: Worldwide, pharmacy practice is changing to include new roles and responsibilities. Laws enabling the implementation of assisted dying are expanding in international jurisdictions. Pharmacy practice in assisted dying is subsequently expanding. However, studies of how pharmacists experience their practice when engaged in assisted dying are absent. To progress research into the lived experiences of pharmacists practicing in assisted dying, the development of an inquiry framework to guide such research is the first step.

Objective: The objective was to develop a theoretical framework of inquiry for use in subsequent continuing research which may explore the actual experience of pharmacy practice in assisted dying.

Methods: Perspectives were gathered from expert and senior pharmacists who were anticipating the imminent implementation of assisted dying practice. Analysis focused on understanding what aspects of practice experience were important to them. Interview-conversations centred on the question: If you had the chance to talk to experienced pharmacist practitioners who have been involved in the practice of assisted dying, what aspects regarding their experiences, would you like to know about? A conventional approach to qualitative content analysis was utilized to analyze the data.

Results: Findings summarized questions posed by pharmacists contemplating the implementation of assisted dying practice. These perspectives formed the foundation of a theoretical inquiry framework constituted by 8 inter-related dimensional range-continuums. Each range-continuum, designed to explore the lived experiences of pharmacists in practice, is defined. Examples of how the inquiry dimensions will be used to inform future exploratory research are offered within the framework.

Conclusions: The theoretical inquiry framework will be used to develop knowledge for pharmacists contemplating participation (or not) in assisted dying practice. It is timely to progress research that reveals the informed experiences of pharmacists that are actually practicing in this area. The framework may be adapted for researching pharmacists' experience in other practice areas and contexts.
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http://dx.doi.org/10.1016/j.sapharm.2020.05.028DOI Listing
June 2020

Hospital pharmacists' ethical exposure and decision-making.

Res Social Adm Pharm 2021 Feb 7;17(2):372-380. Epub 2020 Apr 7.

School of Pharmacy and Pharmacology, Griffith University, 4072, Queensland, Australia; Quality Use of Medicines Network, Griffith University, 4072, Queensland, Australia; Pharmacy Department, Gold Coast Health, 4072, QLD, Australia. Electronic address:

Background: Studies have explored community pharmacy ethical dilemmas; however, limited research exists on hospital pharmacy ethical issues and pharmacists' ethical decision-making processes. Research exploring this is timely, considering developments in hospital pharmacy practices, new hospital pharmacist roles, and evolving responsibilities.

Aim/objectives: To explore hospital pharmacists' ethical decision-making and processes for managing ethical challenges in the context of evolving Australian hospital pharmacy practices.

Methods: Face-to-face semi-structured interviews with 20 purposively-selected hospital pharmacists from four Queensland Health hospitals. An interview guide with 11 open-ended questions and prompts was developed, validated, and trialed. Pharmacists who consented received the guide prior to interviews. Interviews were audio recorded, transcribed verbatim, and compared with field notes. Transcribed data were imported into NVivo 12 to facilitate coding and thematic analysis.

Results: Participants were interviewed January to April 2019; median interview duration was 17.45 min. Data saturation was reached. Participants' experiences ranged from junior level pharmacists to senior management positions, in clinical and non-clinical roles. Emerging themes were: 1) influences on the development of ethical decision-making skills, 2) ethical decision-making is an integral part of the hospital pharmacist's role, and 3) institutional requirements and settings impact on ethical exposure. A wide range of contemporary ethical issues unique to hospital pharmacy practice, mostly involving complex medication management safety, supply, and cost scenarios, were identified. Junior pharmacists indicated they would benefit from additional training, mentorship, and availability of hospital-specific targeted ethics resources.

Conclusion: The findings highlighted that hospital pharmacists are regularly faced with ethical issues unique to the hospital pharmacy practice context. Application of sound and structured ethical reasoning and decision-making is, therefore, required in this setting. Participants identified many interrelated factors that impacted their ethical reasoning and behaviour. This study identified gaps that, once addressed, will better support ethical reasoning in hospital pharmacy settings.
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http://dx.doi.org/10.1016/j.sapharm.2020.03.011DOI Listing
February 2021

Biochemical recovery from exertional heat stroke follows a 16-day time course.

PLoS One 2020 4;15(3):e0229616. Epub 2020 Mar 4.

Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States of America.

Background: The aim of this study was to characterize the time-resolved progression of clinical laboratory disturbances days-following an exertional heat stroke (EHS). Currently, normalization of organ injury clinical biomarker values is the primary indicator of EHS recovery. However, an archetypical biochemical recovery profile following EHS has not been established.

Methods: We performed a retrospective analysis of EHS patient records in US military personnel from 2008-2014 using the Military Health System Data Repository (MDR). We focused on commonly reported clinical laboratory analytes measured on the day of injury and all proceeding follow-up visits.

Results: Over the prescribed period, there were 2,529 EHS episodes treated at 250 unique treatment locations. Laboratory results, including a standardized set of blood, serum and urine assays, were analyzed from 0-340 days following the initial injury. Indicators of acute kidney injury, including serum electrolyte disturbances and abnormal urinalysis findings, were most prevalent on the day of the injury but normalized within 24-48hours (creatinine, blood urea nitrogen, and blood and protein in urine). Muscle damage and liver function-associated markers peaked 0-4 days after injury and persisted outside their respective reference ranges for 2-16 days (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, myoglobin, prothrombin time).

Conclusion: Biochemical recovery from EHS spans a 16-day time course, and markers of end-organ damage exhibit distinct patterns over this period. This analysis underscores the prognostic value of each clinical laboratory analyte and will assist in evaluating EHS patient presentation, injury severity and physiological recovery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229616PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055888PMC
June 2020

Delayed metabolic dysfunction in myocardium following exertional heat stroke in mice.

J Physiol 2020 03 19;598(5):967-985. Epub 2020 Feb 19.

Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA.

Key Points: Exposure to exertional heat stroke (EHS) is associated with increased risk of long-term cardiovascular disorders in humans. We demonstrate that in female mice, severe EHS results in metabolic changes in the myocardium, emerging only after 9-14 days. This was not observed in males that were symptom-limited at much lower exercise levels and heat loads compared to females. At 14 days of recovery in females, there were marked elevations in myocardial free fatty acids, ceramides and diacylglycerols, consistent with development of underlying cardiac abnormalities. Glycolysis shifted towards the pentose phosphate and glycerol-3-phosphate dehydrogenase pathways. There was evidence for oxidative stress, tissue injury and microscopic interstitial inflammation. The tricarboxylic acid cycle and nucleic acid metabolism pathways were also negatively affected. We conclude that exposure to EHS in female mice has the capacity to cause delayed metabolic disorders in the heart that could influence long-term health.

Abstract: Exposure to exertional heat stroke (EHS) is associated with a higher risk of long-term cardiovascular disease in humans. Whether this is a cause-and-effect relationship remains unknown. We studied the potential of EHS to contribute to the development of a 'silent' form of cardiovascular disease using a preclinical mouse model of EHS. Plasma and ventricular myocardial samples were collected over 14 days of recovery. Male and female C57bl/6J mice underwent forced wheel running for 1.5-3 h in a 37.5°C/40% relative humidity until symptom limitation, characterized by CNS dysfunction. They reached peak core temperatures of 42.2 ± 0.3°C. Females ran ∼40% longer, reaching ∼51% greater heat load. Myocardial and plasma samples (n = 8 per group) were obtained between 30 min and 14 days of recovery, analysed using metabolomics/lipidomics platforms and compared to exercise controls. The immediate recovery period revealed an acute energy substrate crisis from which both sexes recovered within 24 h. However, at 9-14 days, the myocardium of female mice developed marked elevations in free fatty acids, ceramides and diacylglycerols. Glycolytic and tricarboxylic acid cycle metabolites revealed bottlenecks in substrate flow, with build-up of intermediate metabolites consistent with oxidative stress and damage. Males exhibited only late stage reductions in acylcarnitines and elevations in acetylcarnitine. Histopathology at 14 days showed interstitial inflammation in the female hearts only. The results demonstrate that the myocardium of female mice is vulnerable to a slowly emerging metabolic disorder following EHS that may harbinger long-term cardiovascular complications. Lack of similar findings in males may reflect their lower heat exposure.
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http://dx.doi.org/10.1113/JP279310DOI Listing
March 2020

Australian pharmacists: ready for increased non-prescription medicines reclassification.

Int J Pharm Pract 2020 Jun 8;28(3):246-254. Epub 2020 Jan 8.

School of Pharmacy and Pharmacology, Quality Use of Medicines Network, and Menzies Health Institute Queensland, Griffith University, Queensland, Australia.

Objectives: Reclassification of medicines from prescription to non-prescription increases timely access to treatment, promotes self-management of minor ailments and relieves healthcare system burden. Previous research identified that Australia lagged behind the United Kingdom and New Zealand in medicines reclassification. This study aimed to identify Australian pharmacists' opinions on the current state of medicines reclassification; the prescription medicines consumers requested without prescription; the medicines pharmacists believed should and should not be considered for reclassification; and perceived barriers to reclassification.

Methods: A 2016 national online survey that sought pharmacists' opinions on the state of reclassification, perceived barriers to reclassification and readiness of the profession for further reclassification. Pharmacists' comments were invited through open-ended questions.

Key Findings: Two hundred and thirty-five valid surveys were completed. Respondents practised in community, hospital, consultant and academic contexts, and the majority were female (58.7%, n = 138). More than two thirds (70.66%, n = 166) of pharmacists reported receiving daily or weekly requests for non-prescription access to prescription medicines. The majority of pharmacists (71.7%) agreed that the Australian pharmacy profession is ready for further medicines reclassification, guided by patient safety, harm minimisation and medication continuance. The most prominent barrier to further reclassification was opposition from other healthcare professionals.

Conclusions: Australian pharmacists believe that their profession has the capacity to safely and effectively manage a wider range of non-prescription medicines through increased reclassification in the contexts of patient safety and risk mitigation. This study has contributed to the global conversation on non-prescription medicines access, providing momentum for practice and policy change.
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http://dx.doi.org/10.1111/ijpp.12594DOI Listing
June 2020

Transcription-induced formation of extrachromosomal DNA during yeast ageing.

PLoS Biol 2019 12 3;17(12):e3000471. Epub 2019 Dec 3.

Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom.

Extrachromosomal circular DNA (eccDNA) facilitates adaptive evolution by allowing rapid and extensive gene copy number variation and is implicated in the pathology of cancer and ageing. Here, we demonstrate that yeast aged under environmental copper accumulate high levels of eccDNA containing the copper-resistance gene CUP1. Transcription of the tandemly repeated CUP1 gene causes CUP1 eccDNA accumulation, which occurs in the absence of phenotypic selection. We have developed a sensitive and quantitative eccDNA sequencing pipeline that reveals CUP1 eccDNA accumulation on copper exposure to be exquisitely site specific, with no other detectable changes across the eccDNA complement. eccDNA forms de novo from the CUP1 locus through processing of DNA double-strand breaks (DSBs) by Sae2, Mre11 and Mus81, and genome-wide analyses show that other protein coding eccDNA species in aged yeast share a similar biogenesis pathway. Although abundant, we find that CUP1 eccDNA does not replicate efficiently, and high-copy numbers in aged cells arise through frequent formation events combined with asymmetric DNA segregation. The transcriptional stimulation of CUP1 eccDNA formation shows that age-linked genetic change varies with transcription pattern, resulting in gene copy number profiles tailored by environment.
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http://dx.doi.org/10.1371/journal.pbio.3000471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890164PMC
December 2019

Calcium Regulation of Bacterial Virulence.

Adv Exp Med Biol 2020 ;1131:827-855

Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK, USA.

Calcium (Ca) is a universal signaling ion, whose major informational role shaped the evolution of signaling pathways, enabling cellular communications and responsiveness to both the intracellular and extracellular environments. Elaborate Ca regulatory networks have been well characterized in eukaryotic cells, where Ca regulates a number of essential cellular processes, ranging from cell division, transport and motility, to apoptosis and pathogenesis. However, in bacteria, the knowledge on Ca signaling is still fragmentary. This is complicated by the large variability of environments that bacteria inhabit with diverse levels of Ca. Yet another complication arises when bacterial pathogens invade a host and become exposed to different levels of Ca that (1) are tightly regulated by the host, (2) control host defenses including immune responses to bacterial infections, and (3) become impaired during diseases. The invading pathogens evolved to recognize and respond to the host Ca, triggering the molecular mechanisms of adhesion, biofilm formation, host cellular damage, and host-defense resistance, processes enabling the development of persistent infections. In this review, we discuss: (1) Ca as a determinant of a host environment for invading bacterial pathogens, (2) the role of Ca in regulating main events of host colonization and bacterial virulence, and (3) the molecular mechanisms of Ca signaling in bacterial pathogens.
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http://dx.doi.org/10.1007/978-3-030-12457-1_33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473484PMC
October 2019

Multi-disciplinary interventions for chronic pain involving education: A systematic review.

PLoS One 2019 2;14(10):e0223306. Epub 2019 Oct 2.

School of Pharmacy and Pharmacology, Menzies Health Institute Queensland, Griffith University, Queensland, Australia.

Background: There have been growing recommendations to include education in multi-disciplinary interventions targeting chronic pain management. However, effects of this strategy on short- and long-term self-management of chronic pain, remain largely unexplored.

Objectives: 1. To provide an updated overview of studies that report on the impact of patient education in multi-disciplinary interventions, on self-management of chronic pain; 2. To explore associations between education and chronic pain self-management techniques; and 3. To identify the format and duration of suitable chronic pain interventions targeted at patient self-management.

Methods: Design: Narrative systematic literature review of randomised or controlled study designs. Data Sources: PubMed, CINAHL, EMBASE, PsycINFO. Participants: Adult patients with chronic pain of any aetiology participating in multi-disciplinary programs that included education. Main outcome measures: Assessments of level of pain, function, quality of life, self-efficacy, self-management, and any other relevant assessments. Study Appraisal and Synthesis Methods: PRISMA guidelines, Cochrane Risk of Bias tool, and TIDieR model.

Results: Database searching identified 485 potential papers. After removal of duplicates, and irrelevant articles by title and abstract, 120 full-text articles were reviewed and 27 studies were included in this systematic review. Studies were predominantly from the United States (n = 8; 29.6%). Over one hundred outcome measures were identified across all studies, with significant variation also observed in terms of how chronic pain duration was defined, and how education was delivered to participants. Overall, positive benefits of education were reported.

Conclusions: Education, as part of multi-disciplinary programs, is likely to improve self-management and self-efficacy in people with chronic pain of any aetiology. Heterogeneity in terms of: chronic pain duration; educational resources; healthcare professionals; and outcome measures, were identified as limitations. Further research, in the form of Randomised Controlled Trials addressing these limitations, is recommended.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223306PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774525PMC
March 2020

Influence of prior illness on exertional heat stroke presentation and outcome.

PLoS One 2019 20;14(8):e0221329. Epub 2019 Aug 20.

Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States of America.

Introduction: Precipitating factors that contribute to the severity of exertional heat stroke (EHS) are unclear. The purpose of this study was to determine the effect of prior illness (PI) on EHS severity.

Methods: We performed a retrospective clinical record review of 179 documented cases of EHS at the Marine Corps Base in Quantico, Virginia.

Results: Approximately 30% of EHS cases had a medically documented PI. Anthropometrics (height, weight, body mass index) and commonly associated risk factors for EHS (age, number of days in training, wet bulb globe temperature, sleep patterns) did not differ between PI and no illness (NI) groups. PI patients presented with higher maximal rectal core temperatures (40.6 ± 1.0°C vs. 40.3 ± 1.2°C; P = 0.0419), and elevated pulse rates (118.1 ± 16.7 bpm vs. 110.5 ± 24.2 bpm; P = 0.0397). At the point of care, biomarker values were similar between PI and NI groups, with the exception of a trend toward elevated monocytes in those with PI (7.9 ± 2.9% vs 6.7± 2.7%; P = 0.0521). Rate and duration of cooling were similar between PI and NI patients.

Conclusion: This study indicates that PI has a minimal effect on the patient presentation, severity and treatment outcome of EHS. The results of this study have important implications for military, civilian, and occupational populations who are at risk for EHS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221329PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701802PMC
April 2020

Use of the heat tolerance test to assess recovery from exertional heat stroke.

Temperature (Austin) 2019 9;6(2):106-119. Epub 2019 Feb 9.

U.S. Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, Massachusetts.

Exercise or work in hot environments increases susceptibility to exertional heat illnesses such as exertional heat stroke (EHS). EHS occurs when body heat gain exceeds body heat dissipation, resulting in rapid body heat storage and potentially life-threatening consequences. EHS poses a dangerous threat for athletes, agriculture workers, and military personnel, as they are often exposed to hot environmental conditions that restrict body heat loss or contribute to body heat gain. Currently, there is limited guidance on return to activity (RTA) after an episode of EHS. While examining biomarkers in the blood is thought to be beneficial for determining RTA, they are not sensitive or specific enough to be a final determining factor as organ damage may persist despite blood biomarkers returning to baseline levels. As such, additional assessment tests to more accurately determine RTA are desired. One method used for determining RTA is the heat tolerance test (HTT, 120 minutes treadmill walking; 40°C, 40% relative humidity). Unfortunately, the HTT provides even less information about EHS recovery since it offers no test sensitivity or specificity even after years of implementation. We provide an overview of the HTT and the controversy of this test with respect to assessment criteria, applicability to tasks involving high metabolic workloads, and the lack of follow-up analyses to determine its accuracy for determining recovery in order to diminish the likelihood of a second EHS occurrence.
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http://dx.doi.org/10.1080/23328940.2019.1574199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601408PMC
February 2019

MicroRNA-1-Mediated Inhibition of Cardiac Fibroblast Proliferation Through Targeting Cyclin D2 and CDK6.

Front Cardiovasc Med 2019 17;6:65. Epub 2019 May 17.

Cardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, United States.

MicroRNA-1 (miRNA-1) has been long viewed as a muscle-specific miRNA and plays a critical role in myocardium and cardiomyocytes by controlling myocyte growth and rhythm. We identified that miRNA-1 is expressed in cardiac fibroblasts, which are one of the major non-muscle cell types in myocardium and are responsible for cardiac fibrosis in pathological conditions. In this study, we aimed to investigate the effect and mechanism of action of miRNA-1 on cardiac fibroblast proliferation. Subcutaneous angiotensin II (Ang II) infusion via osmotic minipumps for 4 weeks was used to induce myocardial interstitial fibrosis in male Sprague-Dawley rats. MiRNA-1 expression was significantly down-regulated by 68% in freshly isolated ventricular fibroblasts from Ang II-infused rats than that from control rats. Similar results were obtained in adult rat ventricular fibroblasts that were stimulated in culture by Ang II or TGFβ for 48 h. Functionally, overexpression of miRNA-1 inhibited fibroblast proliferation, whereas knockdown of endogenous miRNA-1 increased fibroblast proliferation. We then identified and validated cyclin D2 and cyclin-dependent kinase 6 (CDK6) as direct targets of miRNA-1 in cardiac fibroblasts using biochemical assays. Moreover, we showed that the inhibitory effects of miRNA-1 on cardiac fibroblast proliferation can be blunted by overexpression of its target, cyclin D2. In conclusion, our findings demonstrate miRNA-1 expression and regulation in adult ventricular fibroblasts, where it acts as a novel negative regulator of adult cardiac fibroblast proliferation that is at least partially mediated by direct targeting of two cell cycle regulators. Our results expand the understanding of the regulatory roles of miRNA-1 in cardiac cells (i.e., from myocytes to a major non-muscle cells in the heart).
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http://dx.doi.org/10.3389/fcvm.2019.00065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533459PMC
May 2019

Pharmacy practice in the domain of assisted dying: A mapping review of the literature.

Res Social Adm Pharm 2020 Mar 20;16(3):267-276. Epub 2019 May 20.

Menzies Health Institute Queensland, Griffith Institute for the Development of Education and Scholarship (Health IDEAS), School of Pharmacy and Pharmacology, Griffith University, Australia. Electronic address:

Background: The scope and roles of pharmacists worldwide are undergoing dramatic change. Patient-focused care aimed at caring for people that seek medical assistance in dying is among the newest roles. While pharmacists have been involved in medically assisted dying in some international jurisdictions for over two decades, little is known about their actual lived experiences.

Objective: To map the literature concerning pharmacy practice in the assisted dying domain to clarify apparent research gaps.

Methods: A mapping review was preformed following a systematic search of Medline, CINAHL and IPA to locate academic papers and reports relating to pharmacists' involvement in assisted dying published between 1990 and 2019. Searches included articles in English, French, and Dutch. References and citations of articles were searched to identify additional articles.

Results: A total of 43 articles were selected, including commentaries (n = 26), reports (n = 2), a scoping literature review (n = 1), and empirical studies (n = 14). Most commentaries centered on pharmacists' roles, ethico-legal and moral challenges, and educational concerns in relation to participation. Of the 14 empirical studies, 12 studies were designed around surveys that focused on pharmacists' attitudes, and opinions concerning assisted dying. Other methodologies included thematic analysis of moral dilemmas, experimental design identifying attitudes to sedation at end of life, and analysis of documents such as guidelines, position statements, and standards of practice. Two studies utilized a qualitative research approach. A significant gap was found with respect to research exploring the actual experience of pharmacists' practice in medically assisted dying.

Conclusion: There is an absence of studies exploring pharmacists' actual experiences in assisted dying practice. Research involving pharmacists that participate in legally sanctioned assisted dying will facilitate a meaningful understanding of the lived experience of pharmacy practice in this domain.
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http://dx.doi.org/10.1016/j.sapharm.2019.05.012DOI Listing
March 2020

Pharmacy ethical reasoning: a comparison of Australian pharmacists and interns.

Int J Clin Pharm 2019 Aug 15;41(4):1085-1098. Epub 2019 May 15.

School of Pharmacy and Pharmacology, Griffith University, Clinical Sciences 2, G16_3.26, Gold Coast Campus, Gold Coast, QLD, 4215, Australia.

Background Ethical reasoning informs decision making and professional judgement, is guided by codes of ethics and conduct, and requires navigation through a regulatory framework. Ethical reasoning should evolve throughout the pharmacy internship year and prepare interns for independent practice. Objective To explore the ethical reasoning and processes of Australian pharmacists and pharmacy interns. Setting Queensland community pharmacists and interns. Method A survey to determine use of resources to guide ethical decisions, management of ethical dilemmas, and exposure to potential practice privacy breaches. Participants were recruited at pharmacy intern training events, a pharmacist education session and through telephone contact of randomised community pharmacies. Main outcome measure Comparison between pharmacist and intern responses using 5-point Likert scales, listings and prioritising. Results In total 218 completed surveys were analysed: 121 pharmacy interns and 97 pharmacists. The Code of Ethics was identified as the resource most frequently consulted when faced with ethical dilemmas. Interns were more likely to consult legislation and regulatory authorities whereas pharmacists with colleagues. Responses to ethical vignette scenarios and exposure to privacy breaches varied between interns and pharmacists, with some scenarios revealing significant differences. Most participants had been exposed to a variety of potential privacy breaches in practice. Conclusion Interns focussed on legislation and guidelines when presented with hypothetical ethical dilemmas. In contrast to this positivist approach, pharmacists reported using a social constructionist approach with peers as a reference. Pharmacists avoided ethical scenario options that required complex management. Interns reported more exposure to potential practice privacy breaches.
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http://dx.doi.org/10.1007/s11096-019-00815-5DOI Listing
August 2019

Turning Pain into Gain: Evaluation of a Multidisciplinary Chronic Pain Management Program in Primary Care.

Pain Med 2019 05;20(5):925-933

School of Pharmacy and Pharmacology, Gold Coast Campus, Griffith University, Queensland 4222, Australia and Menzies Health Institute Queensland, Gold Coast Campus, Griffith University, Queensland, Australia.

Objective: To measure the impact of the multidisciplinary Turning Pain Into Gain program in people experiencing chronic pain of any etiology.

Methods: A mixed-methods observational study of 252 participants was used to explore the impact of Turning Pain Into Gain on medication use; quality of life and functioning, as measured by the Pain Self-Efficacy Questionnaire; and self-reported hospitalizations between 2015 and 2016.

Results: Responses from 178 participants showed an increased alignment with Australian pain medication guidelines (e.g., a 7.3% reduction in paracetamol duplication was reported with a concurrent 5.1% rise in the administration of sustained-release paracetamol formulations); improved Pain Self-Efficacy Questionnaire scores from 23.1 (out of a possible score of 60) preprogram to 35.3 postprogram; and a reduction in self-reported hospitalizations from 50 cases in the 12 months preprogram to 11 cases in the 12 months postprogram.

Conclusions: Positive medication, Pain Self-Efficacy Questionnaire, and hospitalization changes provide evidence for the broader implementation of similar patient-centered programs to promote more holistic management of diverse types of chronic pain in primary care. Reduced hospitalization reflects potential for this intervention to be cost-effective, which could be investigated further.
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http://dx.doi.org/10.1093/pm/pny241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497132PMC
May 2019

Turning Pain into Gain: Evaluation of a Multidisciplinary Chronic Pain Management Program in Primary Care.

Pain Med 2019 05;20(5):925-933

School of Pharmacy and Pharmacology, Gold Coast Campus, Griffith University, Queensland 4222, Australia and Menzies Health Institute Queensland, Gold Coast Campus, Griffith University, Queensland, Australia.

Objective: To measure the impact of the multidisciplinary Turning Pain Into Gain program in people experiencing chronic pain of any etiology.

Methods: A mixed-methods observational study of 252 participants was used to explore the impact of Turning Pain Into Gain on medication use; quality of life and functioning, as measured by the Pain Self-Efficacy Questionnaire; and self-reported hospitalizations between 2015 and 2016.

Results: Responses from 178 participants showed an increased alignment with Australian pain medication guidelines (e.g., a 7.3% reduction in paracetamol duplication was reported with a concurrent 5.1% rise in the administration of sustained-release paracetamol formulations); improved Pain Self-Efficacy Questionnaire scores from 23.1 (out of a possible score of 60) preprogram to 35.3 postprogram; and a reduction in self-reported hospitalizations from 50 cases in the 12 months preprogram to 11 cases in the 12 months postprogram.

Conclusions: Positive medication, Pain Self-Efficacy Questionnaire, and hospitalization changes provide evidence for the broader implementation of similar patient-centered programs to promote more holistic management of diverse types of chronic pain in primary care. Reduced hospitalization reflects potential for this intervention to be cost-effective, which could be investigated further.
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http://dx.doi.org/10.1093/pm/pny241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497132PMC
May 2019

Australian pharmacy perspectives on increasing access to medicines through reclassification.

J Health Serv Res Policy 2019 04 23;24(2):81-90. Epub 2018 Oct 23.

7 Lecturer, School of Pharmacy and Pharmacology, Quality Use of Medicines Network, Menzies Health Institute Queensland, Griffith University, Australia.

Objectives: Availability of medicines without prescription can increase consumers' timely access to treatment and promote self-management of minor ailments and adherence to long-term medications. Globally, access to relevant medicines has improved through increased reclassification of medicines from prescription to non-prescription availability. However, Australian reclassification lags behind countries with comparable health systems, and the factors influencing this are poorly understood.

Methods: Semi-structured interviews were conducted during May 2015 to explore the perspectives of Australian pharmacists and support staff on future reclassification. Interview responses were transcribed verbatim, and the data were analysed thematically, primarily informed by the general inductive approach.

Results: Participants identified a broad range of medicines as candidates for future reclassification by applying risk versus benefit judgements, assessing any medicines with potential for misuse and hazardous medicines as unsuitable. Key drivers for change in classification were underpinned by participants' desire to support consumers' management of minor ailments and adherence for those on long-term therapy. Barriers to reclassification were identified by pharmacy staff as internal, negatively impacting pharmacists' readiness for reclassification and external, negatively impacting the overall progress of change.

Conclusions: While the research provided valuable insights to inform the ongoing discussion on future reclassification, a larger, more representative sample is needed to confirm these findings.
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http://dx.doi.org/10.1177/1355819618799112DOI Listing
April 2019

Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells.

Elife 2018 10 2;7. Epub 2018 Oct 2.

Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom.

Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which methylates histone H3 lysine 4 (H3K4) to form H3K4me1, H3K4me2 and H3K4me3. Here, we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations reduce replicative lifespan and cause expression defects in almost 500 genes. Although H3K4 methylation is reported to act primarily in gene repression, particularly in yeast, repressive functions are progressively lost with age while hundreds of genes become dependent on H3K4me3 for full expression. Basal and inducible expression of these genes is also impaired in young cells lacking COMPASS components Swd1 or Spp1. Gene induction during ageing is associated with increasing promoter H3K4me3, but H3K4me3 also accumulates in non-promoter regions and the ribosomal DNA. Our results provide clear evidence that H3K4me3 is required to maintain normal expression of many genes across organismal lifespan.
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http://dx.doi.org/10.7554/eLife.34081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168286PMC
October 2018

Support for Australian carers from community pharmacy: Insight into carer perspectives of a novel service.

Health Soc Care Community 2019 03 6;27(2):320-329. Epub 2018 Sep 6.

Griffith University, Quality Use of Medicines Network, Menzies Health Institute Queensland, Southport, Queensland, Australia.

The feasibility of an individualised carer support service delivered in community pharmacies was assessed from the perspective of carer participants using a pre-post questionnaire and semistructured interviews. Eligible pharmacies were required to offer a medication management service relevant to carers and have a semiprivate space for conversations. Carers were required to self-identify as an unpaid support person for someone with a chronic condition or disability. Between September 2016 and March 2017, staff from 11 community pharmacies in South-East Queensland, Australia were trained, and provided with ongoing mentoring from a pharmacist and carer to support service implementation. Identification of carers and support to achieve a personal and care-giving goal were key features of the service. Questionnaires included the EQ-5D-3L, the Bakas Caregiving Outcomes Scale, and questions relating to goal achievement, carer roles, and responsibilities. Seven follow-up carer interviews were undertaken between March and May 2017 and analysed thematically. Pre-post questionnaires were available for 17 carers (one withdrew, two incomplete). Of the 29 goals set, 10 were achieved and 14 partially achieved. EQ-5D-3L scores were unchanged, while 7 of the 15 items comprising the Bakas score improved (p < 0.05). Carer service evaluation was generally favourable, and these two main interview themes were the impact of caring and pharmacy experience. The impact of caring, while variable, was significant. Pharmacy experiences were mostly positive and the opportunity for carers to further engage with pharmacy staff was appreciated. The service was feasible and initial reported benefits to carers may support further research potentially in terms of a larger controlled trial.
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http://dx.doi.org/10.1111/hsc.12649DOI Listing
March 2019

Sex-dependent responses to exertional heat stroke in mice.

J Appl Physiol (1985) 2018 09 14;125(3):841-849. Epub 2018 Jun 14.

Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, Florida.

With increasing participation of females in endurance athletics and active military service, it is important to determine if there are inherent sex-dependent susceptibilities to exertional heat injury or heat stroke. In this study we compared responses of male and female adult mice to exertional heat stroke (EHS). All mice were instrumented for telemetry core temperature measurements and were exercise-trained for 3 wk before EHS. During EHS, environmental temperature was 37.5°C (35% RH) while the mice ran on a forced running wheel, using incremental increases in speed. The symptom-limited endpoint was loss of consciousness, occurring at ~42.2°C core temperature. Females ran greater distances (623 vs. 346 m, P < 0.0001), reached faster running speeds (7.2 vs. 5.1 m/min, P < 0.0001), exercised for longer times (177 vs. 124 min, P < 0.0001), and were exposed to greater internal heat loads (240 vs.160°C·min; P < 0.0001). Minimum Tc during hypothermic recovery was ~32.0°C in both sexes. Females lost 9.2% body weight vs. 7.5% in males ( P < 0.001). Females demonstrated higher circulating corticosterone (286 vs 183 ng/ml, P = 0.001, at 3 h), but most plasma cytokines were not different. A component of performance in females could be attributed to greater body surface area/mass and greater external power performance. However, there were significant and independent effects of sex alone and a crossed effect of "sex × power" on performance. These results demonstrate that female mice have greater resistance to EHS during exercise in hyperthermia and that these effects cannot be attributed solely to body size. NEW & NOTEWORTHY Female mice are surprisingly more resistant to exertional heat stroke than male mice. They run faster and longer and can withstand greater internal heat loads. These changes cannot be fully accounted for by increased body surface/mass ratio in females or on differences in aerobic performance. Although the stress-immune response in males and females was similar, females exhibited markedly higher plasma corticosteroid levels, which were sustained over 14 days of recovery.
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http://dx.doi.org/10.1152/japplphysiol.00220.2018DOI Listing
September 2018

A pharmacy carer support service: obtaining new insight into carers in the community.

Int J Pharm Pract 2019 Feb 6;27(1):34-44. Epub 2018 May 6.

Quality Use of Medicines Network, Menzies Health Institute Queensland, Griffith University, Logan Campus, Meadowbrook, Qld, Australia.

Objectives: Unpaid carers have many and varied responsibilities in society, which can include medication management for the person they support. However, the potential for Australian community pharmacies to better assist carers is relatively unexplored. This mixed-methods study investigated the acceptability of a local carer support service by trained community pharmacy staff, including issues regarding the implementation and impact of this service.

Methods: Staff from 11 community pharmacies in South East Queensland, Australia, were trained to deliver a six-step carer support service between September 2016 and March 2017. Pharmacies were supported by a carer and pharmacist mentor pair and asked to recruit up to six carers each. Evaluations of staff training were descriptively analysed. Semi-structured interviews were undertaken with pharmacy staff, and interview transcripts were analysed thematically.

Key Findings: Staff training evaluations were positive; participants acquired new information about carers and rated the service highly in terms of its importance within the pharmacy setting. Feedback was obtained on how to improve the training, such as further opportunities for role-play. Seven staff members were interviewed, and data analysis revealed two main themes: (1) implementation of the carer support service and (2) perceived impact on pharmacy staff. Positive attitudes towards recognising and supporting carers, and training and mentoring were identified with community pharmacies viewed as a suitable place for delivering this new service. New insights into the impact of caring were widely reported, which staff had not appreciated from previous carer interactions. Structural issues, including space and time pressures, and a lack of awareness about the types of support currently available to carers were emphasised.

Conclusion: Pharmacy staff are well positioned to support carers. Engaging carers in conversation to better understand their needs is a small step with potential for big gains, including a more empathetic understanding of their individual circumstances and overall well-being.
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http://dx.doi.org/10.1111/ijpp.12454DOI Listing
February 2019

Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts.

PLoS One 2018 1;13(5):e0196714. Epub 2018 May 1.

Cardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, United States of America.

Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196714PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929561PMC
July 2018

Protein kinase D activation induces mitochondrial fragmentation and dysfunction in cardiomyocytes.

J Physiol 2018 03 25;596(5):827-855. Epub 2018 Jan 25.

Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA.

Key Points: Abnormal mitochondrial morphology and function in cardiomyocytes are frequently observed under persistent G protein-coupled receptor (G PCR) stimulation. Cardiac signalling mechanisms for regulating mitochondrial morphology and function under pathophysiological conditions in the heart are still poorly understood. We demonstrate that a downstream kinase of G PCR, protein kinase D (PKD) induces mitochondrial fragmentation via phosphorylation of dynamin-like protein 1 (DLP1), a mitochondrial fission protein. The fragmented mitochondria enhance reactive oxygen species generation and permeability transition pore opening in mitochondria, which initiate apoptotic signalling activation. This study identifies a novel PKD-specific substrate in cardiac mitochondria and uncovers the role of PKD on cardiac mitochondria, with special emphasis on the molecular mechanism(s) underlying mitochondrial injury with abnormal mitochondrial morphology under persistent G PCR stimulation. These findings provide new insights into the molecular basis of cardiac mitochondrial physiology and pathophysiology, linking G PCR signalling with the regulation of mitochondrial morphology and function.

Abstract: Regulation of mitochondrial morphology is crucial for the maintenance of physiological functions in many cell types including cardiomyocytes. Small and fragmented mitochondria are frequently observed in pathological conditions, but it is still unclear which cardiac signalling pathway is responsible for regulating the abnormal mitochondrial morphology in cardiomyocytes. Here we demonstrate that a downstream kinase of G protein-coupled receptor (G PCR) signalling, protein kinase D (PKD), mediates pathophysiological modifications in mitochondrial morphology and function, which consequently contribute to the activation of apoptotic signalling. We show that G PCR stimulation induced by α -adrenergic stimulation mediates mitochondrial fragmentation in a fission- and PKD-dependent manner in H9c2 cardiac myoblasts and rat neonatal cardiomyocytes. Upon G PCR stimulation, PKD translocates from the cytoplasm to the outer mitochondrial membrane (OMM) and phosphorylates a mitochondrial fission protein, dynamin-like protein 1 (DLP1), at S637. PKD-dependent phosphorylation of DLP1 initiates DLP1 association with the OMM, which then enhances mitochondrial fragmentation, mitochondrial superoxide generation, mitochondrial permeability transition pore opening and apoptotic signalling. Finally, we demonstrate that DLP1 phosphorylation at S637 by PKD occurs in vivo using ventricular tissues from transgenic mice with cardiac-specific overexpression of constitutively active Gα protein. In conclusion, G PCR-PKD signalling induces mitochondrial fragmentation and dysfunction via PKD-dependent DLP1 phosphorylation in cardiomyocytes. This study is the first to identify a novel PKD-specific substrate, DLP1 in mitochondria, as well as the functional role of PKD in cardiac mitochondria. Elucidation of these molecular mechanisms by which PKD-dependent enhanced fission mediates cardiac mitochondrial injury will provide novel insight into the relationship among mitochondrial form, function and G PCR signalling.
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http://dx.doi.org/10.1113/JP275418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830422PMC
March 2018

The development and piloting of "ATTEND DR," a clinical teaching tool to identify and prioritize potential causes of adverse drug reactions.

Curr Pharm Teach Learn 2017 Jan - Feb;9(1):66-71. Epub 2016 Oct 27.

Menzies Health institute Queensland and School of Pharmacy, Gold Coast Campus, Griffith University, Queensland, Australia; Mater Research Institute, The University of Queensland, South Brisbane, Queensland, Australia.

Background: The identification, management, and reporting of adverse drug reactions are integral to clinical practice and education; however, undergraduate teaching related to adverse drug reactions may be inadequate for practice. Existing methods of causality assessment have a number of limitations in relation to clinical teaching, for example, they do not deal well with the concurrent use of other medications.

Objective: To develop and pilot a teaching tool to guide students through the process of identifying and prioritizing potential causes of an adverse drug reaction.

Setting: University-based School of Pharmacy, Australia: an undergraduate Quality Use of Medicines course.

Method: A contrived acronym (mnemonic) was developed from causality assessments and discussions with practitioners. The acronym ATTEND DR (abnormality, taken, timeline, evidence, nothing else?, dose, dechallenge, and rechallenge) was piloted in workshops that focussed on adverse drug reactions and their management. Students' responses to "What did you find most valuable about today's workshop?" and "How could we improve?" were analyzed.

Results: All attendees responded (65/65). Students indicated that the ATTEND DR acronym was easy to remember, and facilitated causality assessment in a clinical context, due to an easily followed, step-by-step, comprehensive process that was easy to remember. More practice case studies were requested.

Conclusion: The ATTEND DR acronym was designed to address limitations of the existing methods of causality assessment in relation to clinical teaching and preparation of students for future clinical roles. Students responded favorably to its introduction, commenting that it was easily remembered and provided a comprehensive, clinically orientated, step-by-step process.
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http://dx.doi.org/10.1016/j.cptl.2016.08.040DOI Listing
July 2018

Transforming the Workforce From Individual to Collective Competence.

J Contin Educ Nurs 2017 Oct;48(10):440-441

Competent individuals can provide incompetent care if they are not able to function as a team. The current column provides highlights from a presentation given by the authors at this year's Association for Nursing Professional Development annual convention, expanding on the concept of collective competence with real-life situations. J Contin Educ Nurs. 2017;48(10):440-441.
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http://dx.doi.org/10.3928/00220124-20170918-02DOI Listing
October 2017

Susceptibility and Resilience to Posttraumatic Stress Disorder-like Behaviors in Inbred Mice.

Biol Psychiatry 2017 Dec 8;82(12):924-933. Epub 2017 Jul 8.

Department of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida; Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida. Electronic address:

Background: The limited neurobiological understanding of posttraumatic stress disorder (PTSD) has been partially attributed to the need for improved animal models. Stress-enhanced fear learning (SEFL) in rodents recapitulates many PTSD-associated behaviors, including stress-susceptible and stress-resilient subgroups in outbred rats. Identification of subgroups requires additional behavioral phenotyping, a confound to mechanistic studies.

Methods: We employed a SEFL paradigm in inbred male and female C57BL/6 mice that combines acute stress with fear conditioning to precipitate traumatic-like memories. Extinction and long-term retention of extinction were examined after SEFL. Further characterization of SEFL effects on male mice was performed with additional behavioral tests, determination of regional activation by Fos immunofluorescence, and RNA sequencing of the basolateral amygdala.

Results: Stressed animals displayed persistently elevated freezing during extinction. While more uniform in females, SEFL produced male subgroups with differential susceptibility that were identified without posttraining phenotyping. Additional phenotyping of male mice revealed PTSD-associated behaviors, including extinction-resistant fear memory, hyperarousal, generalization, and dysregulated corticosterone in stress-susceptible male mice. Altered Fos activation was also seen in the infralimbic cortex and basolateral amygdala of stress-susceptible male mice after remote memory retrieval. Key behavioral outcomes, including susceptibility, were replicated by two independent laboratories. RNA sequencing of the basolateral amygdala revealed transcriptional divergence between the male subgroups, including genes with reported polymorphic association to patients with PTSD.

Conclusions: This SEFL model provides a tool for development of PTSD therapeutics that is compatible with the growing number of mouse-specific resources. Furthermore, use of an inbred strain allows for investigation into epigenetic mechanisms that are expected to critically regulate susceptibility and resilience.
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http://dx.doi.org/10.1016/j.biopsych.2017.06.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683920PMC
December 2017

Cervical Ectropion May Be a Cause of Desquamative Inflammatory Vaginitis.

Sex Med 2017 Sep 28;5(3):e212-e214. Epub 2017 Apr 28.

The Centers for Vulvovaginal Disorders, Washington, DC, and New York, NY, USA; George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Desquamative inflammatory vaginitis is a poorly understood chronic vaginitis with an unknown etiology. Symptoms of desquamative inflammatory vaginitis include copious yellowish discharge, vulvovaginal discomfort, and dyspareunia. Cervical ectropion, the presence of glandular columnar cells on the ectocervix, has not been reported as a cause of desquamative inflammatory vaginitis. Although cervical ectropion can be a normal clinical finding, it has been reported to cause leukorrhea, metrorrhagia, dyspareunia, and vulvovaginal irritation. Patients with cervical ectropion and desquamative inflammatory vaginitis are frequently misdiagnosed with candidiasis or bacterial vaginosis and repeatedly treated without resolution of symptoms. We report the case of a 34-year-old woman with a 4-year history of profuse yellowish discharge and dyspareunia. Upon presentation, her symptoms and laboratory results met the criteria for desquamative inflammatory vaginitis, but the standard treatments did not provide long-lasting relief. As a last resort, cryotherapy (cryosurgery) of her cervix was performed for treatment of her cervical ectropion, which provided complete resolution of her symptoms. Mitchell L, King M, Brillhart H, Goldstein A. Cervical Ectropion May Be a Cause of Desquamative Inflammatory Vaginitis. Sex Med 2017;5:e212-e214.
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http://dx.doi.org/10.1016/j.esxm.2017.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562466PMC
September 2017

Student Perceptions of Learning Through an International Comparison.

Am J Pharm Educ 2016 Dec;80(10):173

School of Pharmacy, Griffith University, Gold Coast Campus, Queensland, Australia.

To broaden pharmacy students' international perspectives through a teaching and learning method involving international comparison. Four topics within a pharmacy law and practice course were taught in-person by collaborating faculty members representing two international perspectives (Australian and Canadian). The assessed learning objective was for students to be able to synthesize an international comparative analysis that reflected an international perspective. Approximately 70% (n=44) of the class completed an online survey instrument that explored students' perceptions of their own learning. Six domains of inquiry represented in the questionnaire included knowledge development, international perspective, future prospects, personal enjoyment, assessment method, and overall learning experience. Quantitative and qualitative survey results reflected students' strong support for all statements of inquiry. The method involving international comparison, a classroom teaching collaboration and knowledge management using compare-contrast strategy positively influenced student perceptions in a range of ways and was effective in raising international perspectives in the pharmacy curriculum.
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http://dx.doi.org/10.5688/ajpe8010173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289729PMC
December 2016

Gender Differences in Global but Not Targeted Demethylation in iPSC Reprogramming.

Cell Rep 2017 01;18(5):1079-1089

Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK; Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. Electronic address:

Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs) is not known. Here, we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires activation-induced cytidine deaminase (AID)-mediated downregulation of UHRF1 protein, and abolishing demethylation leaves thousands of hypermethylated regions in the iPSC genome. Independently of AID and global demethylation, regulatory regions, particularly ESC enhancers and super-enhancers, are specifically targeted for hypomethylation in association with transcription of the pluripotency network. Our results show that global and targeted DNA demethylation are conserved and distinct reprogramming processes, presumably because of their respective roles in epigenetic memory erasure and in the establishment of cell identity.
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http://dx.doi.org/10.1016/j.celrep.2017.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300890PMC
January 2017