Exploring experiential learning within interprofessional practice education initiatives for pre-licensure healthcare students: a scoping review.

BACKGROUND: Interprofessional collaborative team-based approaches to care in health service delivery has been identified as important to health care reform around the world. Many academic institutions have integrated interprofessional education (IPE) into curricula for pre-licensure students in healthcare disciplines, but few provide formal initiatives for interprofessional practice (IPP). It is recognized that experiential learning (EL) can play a significant role supporting IPP education initiatives; however, little is known of how EL is used within education for IPP in healthcare settings. METHODS: We conducted a scoping review to map peer-reviewed literature describing IPP education initiatives involving EL for pre-licensure students in healthcare disciplines. A literature search was executed in MEDLINE, CINAHL, EMBASE, ERIC, PsycINFO, Scopus, and Social Services Abstracts. After deduplication, two independent reviewers screened titles and abstracts of 5664 records and then 252 full-text articles that yielded 100 articles for data extraction. Data was extracted using an Excel template, and results synthesized for presentation in narrative and tabular formats. RESULTS: The 100 included articles represented 12 countries and IPP education initiatives were described in three main typologies of literature - primary research, program descriptions, and program evaluations. Forty-three articles used a theory, framework, or model for design of their initiatives with only eight specific to EL. A variety of teaching and learning strategies were employed, such as small interprofessional groups of students, team huddles, direct provision of care, and reflective activities, but few initiatives utilized a full EL cycle. A range of perspectives and outcomes were evaluated such as student learning outcomes, including competencies associated with IPP, impacts and perceptions of the IPP initiatives, and others such as client satisfaction. CONCLUSION: Few educational frameworks specific to EL have been used to inform EL teaching and learning strategies to consolidate IPE learning and prepare students for IPP in healthcare settings. Further development and evaluation of existing EL frameworks and models would be beneficial in supporting robust IPP educational initiatives for students in healthcare disciplines. Intentional, thoughtful, and comprehensive use of EL informed by theory can contribute important advances in IPP educational approaches and the preparation of a future health care workforce.

Barriers and facilitators to opioid agonist therapy in rural and remote communities in Canada: an integrative review.

BACKGROUND: People living in rural and remote communities in Canada are often disproportionately impacted by opioid use disorder. When compared to urban centres, rural and remote populations face additional barriers to treatment, including geographical distance as well as chronic shortages of health care professionals. This integrative review of the literature was conducted to explore the facilitators and barriers of OAT in rural and remote Canadian communities. METHODS: A search of the literature identified relevant studies published between 2001 and 2021. RESULTS: The search strategy yielded 26 scholarly peer-reviewed publications, which explored specific barriers and facilitators to rural and remote OAT in Canada, along with two reports and one fact sheet from the grey literature. Most of the scholarly articles were descriptive studies (n = 14) or commentaries (n = 9); there were only three intervention studies. Facilitators and barriers to OAT programs were organized into six themes: intrapersonal/patient factors, social/non-medical program factors, family/social context factors (including community factors), infrastructure/environmental factors, health care provider factors, and system/policy factors. CONCLUSIONS: Although themes in the literature resembled the social-ecological framework, most of the studies focused on the patient-provider dyad. Two of the most compelling studies focused on community factors that positively impacted OAT success and highlighted a holistic approach to care, nested in a community-based holistic model. Further research is required to foster OAT programs in rural and remote communities.

Beyond traditional library spaces: the practicalities of closing hospital libraries and opening a virtual library.

Introduction: The closure of hospital libraries is a noteworthy trend taking place across North America. A Canadian university and its affiliated health authority chose to close eight hospital libraries and merge them into one virtual library service based on changing use of library services, technology and budgetary concerns. This case study describes the processes and considerations both for closing library spaces and transitioning to a new virtual library service. Description: Project management processes efficiently guided the project to completion. These processes included stakeholder consultation, project proposal, timeline, work breakdown structure and project risk analysis. These along with context specific concerns such as closing physical spaces, communication, staffing and licencing issues impacted the successful completion of the project. The hospital libraries were closed and transitioned to a virtual library service within a six-month period. The new virtual library service launched in January 2018 offering document delivery, literature searching, online training and access to electronic resources licensed for health authority staff. Outcomes: Lessons learned during the transition to a virtual library service are shared to provide support for others considering, planning or actively undergoing a similar transition. Discussion: No librarian wants to close one library let alone several. Budgetary factors pressure health sciences libraries to adapt to new fiscal realities. In the health sciences, online availability and patrons desire for access at the bedside result in the need for libraries to respond to patron driven needs. A virtual library service is one response to the alignment of these factors.

The University of Manitoba Psychiatry Toolkit: Development and Evaluation.

OBJECTIVE: The authors developed and measured the subsequent utilization of a web-based point-of-care information tool and meta-search filter, the University of Manitoba Psychiatry Toolkit, as well as conduct an evaluation of its impact on physicians' information seeking. METHODS: Evaluation entailed analysis of toolkit web page utilization data from user visits to the web-based toolkit, as well as an online survey distributed to psychiatrists and resident trainees to assess information gathering behaviors and attitudes regarding various sources of medical information. RESULTS: Electronic resources and colleagues were the preferred sources for gathering health information, while inadequate time and search skills were ranked as important barriers. Age and physician cadre influenced toolkit use. Majority of respondents used the Psychiatry Toolkit to answer a clinical question, and urgency of the clinical problem influenced their decision to use it. CONCLUSIONS: The Psychiatry Toolkit assists psychiatrists and residents in finding answers to clinical questions arising at point-of-care, helping enhance the ongoing educational needs of physicians.

Impaired mitochondrial degradation by autophagy in the skeletal muscle of the aged female interleukin 10 null mouse.

Mitochondrial dysfunction, chronic inflammation and muscle aging are closely linked. Mitochondrial clearance is a process to dampen inflammation and is a critical pre-requisite to mitobiogenesis. The combined effect of aging and chronic inflammation on mitochondrial degradation by autophagy is understudied. In interleukin 10 null mouse (IL-10(tm/tm)), a rodent model of chronic inflammation, we studied the effects of aging and inflammation on mitochondrial clearance. We show that aging in IL-10(tm/tm) is associated with reduced skeletal muscle mitochondrial death signaling and altered formation of autophagosomes, compared to age-matched C57BL/6 controls. Moreover, skeletal muscles of old IL-10(tm/tm) mice have the highest levels of damaged mitochondria with disrupted mitochondrial ultrastructure and autophagosomes compared to all other groups. These observations highlight the interface between chronic inflammation and aging on altered mitochondrial biology in skeletal muscles.

Analysis of a librarian-mediated literature search service.

Librarian-mediated literature searching is a key service provided at medical libraries. This analysis outlines ten years of data on 19,248 literature searches and describes information on the volume and frequency of search requests, time spent per search, databases used, and professional designations of the patron requestors. Combined with information on best practices for expert searching and evaluations of similar services, these findings were used to form recommendations on the improvement and standardization of a literature search service at a large health library system.

Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase IIα.

Mitotic chromosome formation involves a relatively minor condensation of the chromatin volume coupled with a dramatic reorganization into the characteristic "X" shape. Here we report results of a detailed morphological analysis, which revealed that chromokinesin KIF4 cooperated in a parallel pathway with condensin complexes to promote the lateral compaction of chromatid arms. In this analysis, KIF4 and condensin were mutually dependent for their dynamic localization on the chromatid axes. Depletion of either caused sister chromatids to expand and compromised the "intrinsic structure" of the chromosomes (defined in an in vitro assay), with loss of condensin showing stronger effects. Simultaneous depletion of KIF4 and condensin caused complete loss of chromosome morphology. In these experiments, topoisomerase IIα contributed to shaping mitotic chromosomes by promoting the shortening of the chromatid axes and apparently acting in opposition to the actions of KIF4 and condensins. These three proteins are major determinants in shaping the characteristic mitotic chromosome morphology.

Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study.

BACKGROUND: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population. METHODS: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP) to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study. RESULTS: Twenty-five adults (20-70 years of age) with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1) pregabalin followed by placebo or (2) placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5-15). In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint) were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015). CONCLUSION: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.

Evaluation of the interactions between multiwalled carbon nanotubes and Caco-2 cells.

The aim of this study was to determine whether multiwalled carbon nanotubes (MWNCT) are taken up by and are toxic to human intestinal enterocytes using the Caco-2 cell model. Caco-2 cells were exposed to 50 µg/ml MWCNT (oxidized or pristine) for 24 h, and experiments were repeated in the presence of 2.5 mg/L natural organic matter. Cells displayed many of the properties that characterize enterocytes, such as apical microvilli, basolateral basement membrane, and glycogen. The cell monolayers also displayed tight junctions and electrical resistance. Exposure to pristine and oxidized MWCNT, with or without natural organic matter, did not markedly affect viability, which was assessed by measuring activity of released lactate dehydrogenase (LDH) and staining with propidium iodide. Ultrastructural analysis revealed some damage to microvilli colocalized with the MWCNT; however, neither type of MWCNT was taken up by Caco-2 cells. In contrast, pristine and oxidized MWCNT were taken up by the macrophage RAW 264.7 line. Our study suggests that intestinal enterocytes cells do not take up MWCNT.

Nuclear structure and chromosome segregation in Drosophila male meiosis depend on the ubiquitin ligase dTopors.

In many organisms, homolog pairing and synapsis at meiotic prophase depend on interactions between chromosomes and the nuclear membrane. Male Drosophila lack synapsis, but nonetheless, their chromosomes closely associate with the nuclear periphery at prophase I. To explore the functional significance of this association, we characterize mutations in nuclear blebber (nbl), a gene required for both spermatocyte nuclear shape and meiotic chromosome transmission. We demonstrate that nbl corresponds to dtopors, the Drosophila homolog of the mammalian dual ubiquitin/small ubiquitin-related modifier (SUMO) ligase Topors. We show that mutations in dtopors cause abnormalities in lamin localizations, centriole separation, and prophase I chromatin condensation and also cause anaphase I bridges that likely result from unresolved homolog connections. Bridge formation does not require mod(mdg4) in meiosis, suggesting that bridges do not result from misregulation of the male homolog conjunction complex. At the ultrastructural level, we observe disruption of nuclear shape, an uneven perinuclear space, and excess membranous structures. We show that dTopors localizes to the nuclear lamina at prophase, and also transiently to intranuclear foci. As a role of dtopors at gypsy insulator has been reported, we also asked whether these new alleles affected expression of the gypsy-induced mutation ct(6) and found that it was unaltered in dtopors homozygotes. Our results indicate that dTopors is required for germline nuclear structure and meiotic chromosome segregation, but in contrast, is not necessary for gypsy insulator function. We suggest that dtopors plays a structural role in spermatocyte lamina that is critical for multiple aspects of meiotic chromosome transmission.

Identification and characterization of a functional mitochondrial angiotensin system.

The renin-angiotensin (Ang) system regulates multiple physiological functions through Ang II type 1 and type 2 receptors. Prior studies suggest an intracellular pool of Ang II that may be released in an autocrine manner upon stretch to activate surface membrane Ang receptors. Alternatively, an intracellular renin-Ang system has been proposed, with a primary focus on nuclear Ang receptors. A mitochondrial Ang system has not been previously described. Here we report that functional Ang II type 2 receptors are present on mitochondrial inner membranes and are colocalized with endogenous Ang. We demonstrate that activation of the mitochondrial Ang system is coupled to mitochondrial nitric oxide production and can modulate respiration. In addition, we present evidence of age-related changes in mitochondrial Ang receptor expression, i.e., increased mitochondrial Ang II type 1 receptor and decreased type 2 receptor density that is reversed by chronic treatment with the Ang II type 1 receptor blocker losartan. The presence of a functional Ang system in human mitochondria provides a foundation for understanding the interaction between mitochondria and chronic disease states and reveals potential therapeutic targets for optimizing mitochondrial function and decreasing chronic disease burden with aging.

Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activity.

AIMS: It has been well demonstrated that phosphodiesterase-5A (PDE5A) is expressed in smooth muscle cells and plays an important role in regulation of vascular tone. The role of endothelial PDE5A, however, has not been yet characterized. The present study was undertaken to determine the presence, localization, and potential physiologic significance of PDE5A within vascular endothelial cells. METHODS AND RESULTS: We demonstrate primary location of human, mouse, and bovine endothelial PDE5A at or near caveolae. We found that the spatial localization of PDE5A at the level of caveolin-rich lipid rafts allows for a feedback loop between endothelial PDE5A and nitric oxide synthase (NOS3). Treatment of human endothelium with PDE5A inhibitors resulted in a significant increase in NOS3 activity, whereas overexpression of PDE5A using an adenoviral vector, both in vivo and in cell culture, resulted in decreased NOS3 activity and endothelium-dependent vasodilation. The molecular mechanism responsible for these interactions is primarily regulated by cGMP-dependent second messenger. PDE5A overexpression also resulted in a significant decrease in protein kinase 1 (PKG1) activity. Overexpression of PKG1 rapidly activated NOS3, whereas silencing of the PKG1 gene with siRNA inhibited both NOS3 phosphorylation (S1179) and activity, indicating a novel role for PKG1 in direct regulation of NOS3. CONCLUSION: Our data collectively suggest another target for PDE5A inhibition in endothelial dysfunction and provide another physiologic significance for PDE5A in the modulation of endothelial-dependent flow-mediated vasodilation. Using both in vitro and in vivo models, as well as human data, we show that inhibition of endothelial PDE5A improves endothelial function.

Ultrastructure and regulation of lateralized connexin43 in the failing heart.

RATIONALE: Gap junctions mediate cell-to-cell electric coupling of cardiomyocytes. The primary gap junction protein in the working myocardium, connexin43 (Cx43), exhibits increased localization at the lateral membranes of cardiomyocytes in a variety of heart diseases, although the precise location and function of this population is unknown. OBJECTIVE: To define the subcellular location of lateralized gap junctions at the light and electron microscopic level, and further characterize the biochemical regulation of gap junction turnover. METHODS AND RESULTS: By electron microscopy, we characterized gap junctions formed between cardiomyocyte lateral membranes in failing canine ventricular myocardium. These gap junctions were varied in structure and appeared to be extensively internalizing. Internalized gap junctions were incorporated into multilamellar membrane structures, with features characteristic of autophagosomes. Intracellular Cx43 extensively colocalized with the autophagosome marker GFP-LC3 when both proteins were exogenously expressed in HeLa cells, and endogenous Cx43 colocalized with GFP-LC3 in neonatal rat ventricular myocytes. Furthermore, a distinct phosphorylated form of Cx43, as well as the autophagosome-targeted form of LC3 (microtubule-associated protein light chain 3) targeted to lipid rafts in cardiac tissue, and both were increased in heart failure. CONCLUSIONS: Our data demonstrate a previously unrecognized pathway of gap junction internalization and degradation in the heart and identify a cellular pathway with potential therapeutic implications.

Cardiac nitric oxide synthase-1 localization within the cardiomyocyte is accompanied by the adaptor protein, CAPON.

The mechanism(s) regulating nitric oxide synthase-1 (NOS1) localization within the cardiac myocyte in health and disease remains unknown. Here we tested the hypothesis that the PDZ-binding domain interaction between CAPON (carboxy-terminal PDZ ligand of NOS1), a NOS1 adaptor protein and NOS1, contribute to NOS1 localization in specific organelles within cardiomyocytes. Ventricular cardiomyocytes and whole heart homogenates were isolated from sham and post-myocardial infarction (MI) wild-type (C57BL/6) and NOS1(-/-) female mice for quantification of CAPON protein expression levels. NOS1, CAPON, xanthine oxidoreductase and Dexras1, a CAPON binding partner, were all present and enriched in isolated cardiac sarcoplasmic reticulum (SR) fractions. CAPON co-immunoprecipitated with the mu and alpha isoforms of NOS1 in whole heart lysates, and co-localization of CAPON and NOS1 was demonstrated in the SR and mitochondria with dual immuno-gold electron microscopy. Following MI, CAPON and NOS1 both redistributed to caveolae and colocalized with caveolin-3. In addition, following MI, expression level of CAPON remained unchanged and Dexras1 was reduced, CAPON binding to xanthine oxidoreductase was augmented and the plasma membrane calcium ATPase (PMCA) increased. In NOS1 deficient myocytes, CAPON abundance in the SR was reduced, and redistribution to caveolae and PMCA binding after MI was absent. Together these findings support the hypothesis that NOS1 redistribution in injured myocardium requires the formation of a complex with the PDZ adaptor protein CAPON.

A promoter-hijack strategy for conditional shutdown of multiply spliced essential cell cycle genes.

We describe a method for the isolation of conditional knockouts of essential multiply spliced genes in which the entire body of the gene downstream of the ATG start codon is left untouched but can be switched off rapidly and completely by adding tetracycline to the culture medium. The approach centers on a "promoter-hijack" strategy in which the gene's promoter is replaced with a minimal promoter responsive to the tetracycline-repressible transactivator (tTA). Elsewhere in the genome, a cloned fragment of the gene's promoter is used to drive expression of a tTA. Thus, the gene is essentially regulated by its own promoter but through the intermediary tTA. Using this strategy, we generated a conditional knockout of chromokinesin KIF4A, an important mitotic effector protein whose mRNA is multiply spliced and whose cDNA is highly toxic when overexpressed in cells. We used chicken DT40 cells, but the same strategy should be applicable to ES cells and, eventually, to mice.

Implementing best practice pain management in a pediatric hospital.

PURPOSE: This study aims to evaluate the implementation of a comprehensive program to improve pain management practices in a pediatric hospital. METHODS: The pretest posttest design used questionnaires, patient record audits, and postimplementation focus groups with 366 nurses and 8 physicians. RESULTS: Positive changes occurred in the use of pain scales and in valuing good pain management. The program was less effective in improving procedural pain management and pain documentation. PRACTICE IMPLICATIONS: Important program strengths were the "local champions" (Pain Resource Nurses) and the ongoing support and expertise of the pain committee. Systematic evaluation was important to document successes as well as areas requiring further focus.

ERbeta shifts from mitochondria to nucleus during estrogen-induced neoplastic transformation of human breast epithelial cells and is involved in estrogen-induced synthesis of mitochondrial respiratory chain proteins.

Both estrogen receptors (ER) alpha (ERalpha) and beta (ERbeta) are localized in the nucleus, plasma membrane, and mitochondria, where they mediate the different physiological effects of estrogens. It has been observed that the relative subcellular localization of ERs is altered in several cancer cells. We have demonstrated that MCF-10F cells, the immortal and non-tumorigenic human breast epithelial cells (HBEC) that are ERalpha-negative and ERbeta-positive, are transformed in vitro by 17beta-estradiol (E(2)), generating highly invasive cells that are tumorigenic in severe combined immunodeficient mice. E(2)-transformed MCF-10F (trMCF) cells exhibit progressive loss of ductulogenesis, invasive (bsMCF) and tumorigenic (caMCF) phenotypes. Immunolocalization of ERbeta by confocal fluorescent microscopy and electron microscopy revealed that ERbeta is predominantly localized in mitochondria of MCF-10F and trMCF cells. Silencing ERbeta expression with ERbeta-specific small interference RNA (siRNA-ERbeta) markedly diminishes both nuclear and mitochondrial ERbeta in MCF-10F cells. The ERbeta shifts from its predominant localization in the mitochondria of MCF-10F and trMCF cells to the nucleus of bsMCF cells, becoming predominantly nuclear in caMCF cells. Furthermore, we demonstrated that the mitochondrial ERbeta in MCF-10F cells is involved in E(2)-induced expression of mitochondrial DNA (mtDNA)-encoded respiratory chain (MRC) proteins. This is the first report of an association of changes in the subcellular localization of ERbeta with various stages of E(2)-induced transformation of HBEC and a functional role of mitochondrial ERbeta in mediating E(2)-induced MRC protein synthesis. Our findings provide a new insight into one of the potential roles of ERbeta in human breast cancer.

Current awareness in the new millennium: RSS.

Keeping current is essential for both patrons and librarians in the health sciences. We receive electronic and photocopied tables of contents. We subscribe to relevant mailing lists, newspapers and magazines. We review Web sites, books and journals. Our desks are littered with current awareness items that more often get old than read. RSS or "Really Simple Syndication' is a means of organizing and simplifying current awareness efforts. Using RSS feeds from a variety of sources along with aggregator software, librarians can keep up-to-date without the clutter. This article will provide a starting point from which to take advantage of RSS and continue the process of active learning.

Mitochondrial localization of ERalpha and ERbeta in human MCF7 cells.

We observed previously that estrogen treatment increased the transcript levels of several mitochondrial DNA (mtDNA)-encoded genes for mitochondrial respiratory chain (MRC) proteins and MRC activity in rat hepatocytes and human Hep G2 cells. Others have reported detection of estrogen receptors (ER), ERalpha and ERbeta, in mitochondria of rabbit ovarian and uterine tissue. In this study, we have extended these observations. Using cellular fractionation and Western blot with ERalpha- and ERbeta-specific antibodies, we observed that ERalpha and ERbeta are present in mitochondria of human MCF7 cells and that the mitochondrial ERalpha and ERbeta account for 10 and 18%, respectively, of total cellular ERalpha and ERbeta in 17beta-estradiol (E(2))-treated MCF7 cells. We also found that E(2) significantly enhanced the amounts of mitochondrial ERalpha and ERbeta in a time- and concentration-dependent manner and that these effects are accompanied by a significant increase in the transcript levels of mtDNA-encoded genes, i.e., cytochrome c oxidase subunits I and II. Moreover, we demonstrated that these E(2)-mediated effects were inhibited by the pure ER antagonist, ICI-182780, indicating the involvement of ERs. Using immunohistochemistry with confocal microscopy and immunogold electron microscopy, we demonstrated that ERalpha and ERbeta are located within the MCF7 cell mitochondrial matrix. Computer analysis identified a putative internal mitochondrial targeting peptide signal within human ERbeta, suggesting an inherent potential for ERbeta to enter mitochondria. These findings confirm the observations of others and provide additional support for this novel localization of the ERs and for a potentially important role of the ER in the regulation of mtDNA transcription.

Behavioral deficits during early stages of aging in Caenorhabditis elegans result from locomotory deficits possibly linked to muscle frailty.

Many behavioral responses require the coordination of sensory inputs with motor outputs. Aging is associated with progressive declines in both motor function and muscle structure. However, the consequences of age-related motor deficits on behavior have not been clearly defined. Here, we examined the effects of aging on behavior in the nematode, Caenorhabditis elegans. As animals aged, mild locomotory deficits appeared that were sufficient to impair behavioral responses to sensory cues. In contrast, sensory ability appeared well maintained during aging. Age-related behavioral declines were delayed in animals with mutations in the daf-2/insulin-like pathway governing longevity. A decline in muscle tissue integrity was correlated with the onset of age-related behavioral deficits, although significant muscle deterioration was not. Treatment with a muscarinic agonist significantly improved locomotory behavior in aged animals, indicating that improved neuromuscular signaling may be one strategy for reducing the severity of age-related behavioral impairments.