Wisdom and the Bible in Teaching-Learning through Global Service Experiences.

The authors, who are nursing faculty members and leaders at a faith-based institution of higher education, discuss their concept of wisdom and how it guides their teaching and practice. Wisdom is seen by them as a universal humanuniverse living experience that is inspired and cocreated with their faith and understanding of God with others. They apply the concept of wisdom in global service experiences that their institution supports. These experiences strengthen their inherent core whatness as they cocreate what is important in the moment while participating in teaching-learning.

Healthcare in the Himalayan Kingdom of Bhutan: Lessons for the United States and other western healthcare systems.

Bhutan has demonstrated a trajectory of advances in healthcare, while still remaining true to its culture and traditional forms of medicine. Most recently, Bhutan gained international attention when it implemented a strategic Covid-19 vaccination programme that protected a greater percentage of its population than observed in Western industrialised nations. This accomplishment supports the idea that there are lessons from Bhutan to be shared with the rest of the world. In this work, we delineate our observations of the Bhutanese healthcare system, based on field observations in several Bhutanese cities, and results from surveys of Bhutanese physicians. We identify a number of unique practices that influence patient compliance, health education, and access to care in the Bhutanese system, that may be of particular interest and applicability to other healthcare systems. These include housing multiple health services at one location, fully funded medical visits, using non-physician teachers for health education and use of Gross National Happiness (GNH) measures in care.

Traffic influences nutritional quality of roadside plants for monarch caterpillars.

Roadside habitats are increasingly being targeted for restoration and conservation. Roadside habitats often exhibit altered soil and plant chemistry due to pollution from maintenance (e.g. de-icing salt), car deterioration, and exhaust. Roadside plants may attract animals due to elevated levels of sodium or nitrogen, but high concentrations of heavy metals and sodium can be toxic, potentially setting an ecological trap. In this study, we determine how roads influence the chemistry of common milkweed (Asclepias syriaca) as it is the primary roadside host plant for the declining monarch butterfly (Danaus plexippus) in the eastern United States. Even though road salt is applied during the winter, we detect enhanced sodium along roads the following growing season. Road salts increase soil sodium, which in turn elevates host-plant foliar sodium (occasionally to toxic levels in <10% of plants) and sodium content in monarch caterpillars feeding on these plants. Sodium levels of milkweed leaves are highest close to the edge of busy roads. Some heavy metals (lead, zinc) are also elevated in roadside soils or plants. Nitrogen content was affected by adjacent agricultural use, but not traffic volume or proximity to a road. Other potential road pollutants (e.g. nickel) were not elevated in soil or plants. Despite a clear signature of road pollution in the chemistry of milkweed, most plants are likely still suitable for developing monarchs. Nonetheless, restoration investments in snowy regions should prioritize sites with lower-traffic density that are further from the road edge to minimize toxic impacts of high sodium. To extend this research to other insects of conservation concern, future work should characterize the nutritional quality of nectar, pollen, and other species of host-plants in roadside habitats.

Insulin Receptor Associates with Promoters Genome-wide and Regulates Gene Expression.

Insulin receptor (IR) signaling is central to normal metabolic control and dysregulated in prevalent chronic diseases. IR binds insulin at the cell surface and transduces rapid signaling via cytoplasmic kinases. However, mechanisms mediating long-term effects of insulin remain unclear. Here, we show that IR associates with RNA polymerase II in the nucleus, with striking enrichment at promoters genome-wide. The target genes were highly enriched for insulin-related functions including lipid metabolism and protein synthesis and diseases including diabetes, neurodegeneration, and cancer. IR chromatin binding was increased by insulin and impaired in an insulin-resistant disease model. Promoter binding by IR was mediated by coregulator host cell factor-1 (HCF-1) and transcription factors, revealing an HCF-1-dependent pathway for gene regulation by insulin. These results show that IR interacts with transcriptional machinery at promoters and identify a pathway regulating genes linked to insulin's effects in physiology and disease.

Long-term care facility National Healthcare Safety Network enrollment challenges, 2016.

The Centers for Medicare & Medicaid Services has a national goal to increase the number of long-term care facilities reporting Clostridium difficile infection data to the Centers for Disease Control and Prevention. A partnership between the Tennessee Department of Health and the quality improvement organization, Qsource, helped facilitate successful enrollment into the National Healthcare Safety Network for nursing homes in the state of Tennessee.

Use of the Hage framework for theory construction: Factors affecting glucose control in the college-aged student with type 1 diabetes.

This article describes the Hage framework for theory construction and its application to the clinical problem of glycemic control in college-aged students with type 1 diabetes. College-aged students with type 1 diabetes struggle to self-manage their condition. Glycated hemoglobin (HbA1c), if controlled within acceptable limits (6-8%), is associated with the prevention or delay of serious diabetic complications such as kidney and cardiovascular disease. Diabetes educators provide knowledge and skills, but young adults must self-manage their condition on a daily basis, independent of parents. The Hage framework includes five tasks of theory construction: narrowing and naming the concepts, specifying the definitions, creating the theoretical statements, specifying the linkages, and ordering components in preparation for model building. During the process, concepts within the theory were revised as the literature was reviewed, and measures and hypotheses, foundational to research, were generated. We were successful in applying the framework and creating a model of factors affecting glycemic control, emphasizing that physical activity, thought of as a normal part of wellness, can be a two-edged sword producing positive effect but also serious negative effects in some college-aged students with type 1 diabetes. Contextual factors important to self-management in college-aged students are emphasized. The Hage framework, already used to a small extent in nursing curricula, deserves more attention and, because of its generic nature, may be used as a template for theory construction to examine a wide variety of nursing topics.

GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and analyses of a human GPR37L1 variant.

Progressive myoclonus epilepsies (PMEs) are disorders characterized by myoclonic and generalized seizures with progressive neurological deterioration. While several genetic causes for PMEs have been identified, the underlying causes remain unknown for a substantial portion of cases. Here we describe several affected individuals from a large, consanguineous family presenting with a novel PME in which symptoms begin in adolescence and result in death by early adulthood. Whole exome analyses revealed that affected individuals have a homozygous variant in GPR37L1 (c.1047G>T [Lys349Asn]), an orphan G protein-coupled receptor (GPCR) expressed predominantly in the brain. In vitro studies demonstrated that the K349N substitution in Gpr37L1 did not grossly alter receptor expression, surface trafficking or constitutive signaling in transfected cells. However, in vivo studies revealed that a complete loss of Gpr37L1 function in mice results in increased seizure susceptibility. Mice lacking the related receptor Gpr37 also exhibited an increase in seizure susceptibility, while genetic deletion of both receptors resulted in an even more dramatic increase in vulnerability to seizures. These findings provide evidence linking GPR37L1 and GPR37 to seizure etiology and demonstrate an association between a GPR37L1 variant and a novel progressive myoclonus epilepsy.

Promoting Resident Autonomy During Family-Centered Rounds: A Qualitative Study of Resident, Hospitalist, and Subspecialty Physicians.

BACKGROUND: Family-centered rounds (FCR) have become a leading model for pediatric inpatient rounding. Several studies have examined effective teaching strategies during FCR, but none have focused on promoting resident autonomy. OBJECTIVE: The aim of this study was to identify strategies used by attending physicians to promote resident autonomy during FCR. METHODS: We conducted a qualitative study of attending physicians and residents between December 2012 and February 2013 at an academic children's hospital, where FCR is the standard model for inpatient rounds. Attending physicians participated in individual interviews, and residents participated in 1 of 2 focus groups separated by level of training. Focus group and interview transcripts were coded and themed using qualitative content analysis. RESULTS: Ten attending physicians and 14 residents participated in interviews and focus groups. Attending physician behaviors that promoted resident autonomy included setting clear expectations, preforming a prerounds huddle, deliberate positioning, and delegating teaching responsibilities. These were further categorized as occurring during 1 of 4 distinct periods: (1) at the start of the rotation; (2) before daily FCR; (3) during daily FCR; and (4) after daily FCR. CONCLUSIONS: Residents and attending physicians identified similar strategies to promote resident autonomy during FCR. These strategies occurred during several distinct periods that were not limited to rounds. The results suggest strategies for attending physicians to help balance appropriate and safe patient care with developing resident autonomy in the clinical setting.

A Rationally Designed Connector for Assembly of Protein-Functionalized DNA Nanostructures.

We report on the rational engineering of the binding interface of the self-ligating HaloTag protein to generate an optimized linker for DNA nanostructures. Five amino acids positioned around the active-site entry channel for the chlorohexyl ligand (CH) of the HaloTag protein were exchanged for positively charged lysine amino acids to produce the HOB (halo-based oligonucleotide binder) protein. HOB was genetically fused with the enzyme cytochrome P450 BM3, as well as with BMR, the separated reductase domain of BM3. The resulting HOB-fusion proteins revealed significantly improved rates in ligation with CH-modified oligonucleotides and DNA origami nanostructures. These results suggest that the efficient self-assembly of protein-decorated DNA structures can be greatly improved by fine-tuning of the electrostatic interactions between proteins and the negatively charged nucleic acid nanostructures.

Designed DNA Surfaces for in Vitro Modulation of Natural Killer Cells.

Natural killer (NK) cells are at the junction of the innate and the adaptive immune response and play a very important role in host defense against viral infections and cancer. They have numerous cell surface receptors that activate or inhibit various intracellular signaling cascades that are then integrated to determine the functional activity of these cells. Here we present a surface-based approach that aims to tackle the largely unknown molecular mechanisms of signal integration. We use DNA microarrays containing capture oligonucleotides for the DNA-directed immobilization (DDI) of oligonucleotide-tagged αCD16 antibodies as ligands for NK cells. We demonstrate that the resulting surfaces can be gradually tuned in terms of ligand density to trigger the activation of living NK cells, as evidenced by degranulation, the release of cytokines, and intracellular Ca(2+) flux, measured at the level of single cells.

Two Listeria monocytogenes Pseudo-outbreaks Caused by Contaminated Laboratory Culture Media.

Listeriosis is a serious foodborne infection that disproportionately affects elderly adults, pregnant women, newborns, and immunocompromised individuals. Diagnosis is made by culturing Listeria monocytogenes from sterile body fluids or from products of conception. This report describes the investigations of two listeriosis pseudo-outbreaks caused by contaminated laboratory media made from sheep blood.

Chronic loss of noradrenergic tone produces ß-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens.

Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine ß-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in ß-arrestin2 (ßArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of ßArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in ßArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs.

Multiscale Origami Structures as Interface for Cells.

A DNA-based platform was developed to address fundamental aspects of early stages of cell signaling in living cells. By site-directed sorting of differently encoded, protein-decorated DNA origami structures on DNA microarrays, we combine the advantages of the bottom-up self-assembly of protein-DNA nanostructures and top-down micropatterning of solid surfaces to create multiscale origami structures as interface for cells (MOSAIC). In a proof-of-principle, we use this technology to analyze the activation of epidermal growth factor (EGF) receptors in living MCF7 cells using DNA origami structures decorated on their surface with distinctive nanoscale arrangements of EGF ligand entities. MOSAIC holds the potential to present to adhered cells well-defined arrangements of ligands with full control over their number, stoichiometry, and precise nanoscale orientation. It therefore promises novel applications in the life sciences, which cannot be tackled by conventional technologies.

Site-directed, on-surface assembly of DNA nanostructures.

Two-dimensional DNA lattices have been assembled from DNA double-crossover (DX) motifs on DNA-encoded surfaces in a site-specific manner. The lattices contained two types of single-stranded protruding arms pointing into opposite directions of the plane. One type of these protruding arms served to anchor the DNA lattice on the solid support through specific hybridization with surface-bound, complementary capture oligomers. The other type of arms allowed for further attachment of DNA-tethered probe molecules on the opposite side of the lattices exposed to the solution. Site-specific lattice assembly and attachment of fluorophore-labeled oligonucleotides and DNA-protein conjugates was demonstrated using DNA microarrays on flat, transparent mica substrates. Owing to their programmable orientation and addressability over a broad dynamic range from the nanometer to the millimeter length scale, such supramolecular architecture might be used for presenting biomolecules on surfaces, for instance, in biosensor applications.

The Importance of Situational Awareness: A Qualitative Study of Family Members' and Nurses' Perspectives on Teaching During Family-Centered Rounds.

PURPOSE: Family-centered rounds (FCR) has become a leading model for pediatric inpatient rounding. During FCR, faculty must balance trainees' educational needs with patient care priorities. Investigators have examined trainees' views on effective teaching during FCR, but none have evaluated what family members and nurses consider to be effective teaching behaviors of attending physicians. The authors sought to explore family members' and nurses' perspectives on effective teaching behaviors during FCR. METHOD: The authors conducted (2012-2013) a qualitative study of families and nurses at an academic children's hospital where FCR is the standard model for inpatient rounds. Nurses and families familiar with FCR participated in separate focus groups. The authors reviewed focus group transcripts using techniques of qualitative content analysis; they generated codes and developed categories, supported by illustrative quotations. RESULTS: Fifteen nurses and 13 family members participated in the focus groups. The unifying theme was that situational awareness on behalf of the attending physician is essential for FCR to be educational for all participants. The authors identified four categories of awareness-(1) cognitive factors, (2) logistics and time management, (3) physical environment, (4) emotional state-and developed a set of effective teaching strategies based on participants' comments. CONCLUSIONS: The findings of this study support previous work identifying effective FCR teaching strategies, but this study is the first to include the perspectives of families and nurses. The inclusion of these participants provides a framework for faculty development and training to improve the educational value of FCR.

DNA-Directed Assembly of Capture Tools for Constitutional Studies of Large Protein Complexes.

Large supramolecular protein complexes, such as the molecular machinery involved in gene regulation, cell signaling, or cell division, are key in all fundamental processes of life. Detailed elucidation of structure and dynamics of such complexes can be achieved by reverse-engineering parts of the complexes in order to probe their interactions with distinctive binding partners in vitro. The exploitation of DNA nanostructures to mimic partially assembled supramolecular protein complexes in which the presence and state of two or more proteins are decisive for binding of additional building blocks is reported here. To this end, four-way DNA Holliday junction motifs bearing a fluorescein and a biotin tag, for tracking and affinity capture, respectively, are site-specifically functionalized with centromeric protein (CENP) C and CENP-T. The latter serves as baits for binding of the so-called KMN component, thereby mimicking early stages of the assembly of kinetochores, structures that mediate and control the attachment of microtubules to chromosomes in the spindle apparatus. Results from pull-down experiments are consistent with the hypothesis that CENP-C and CENP-T may bind cooperatively to the KMN network.

Reversible reconfiguration of DNA origami nanochambers monitored by single-molecule FRET.

Today, DNA nanotechnology is one of the methods of choice to achieve spatiotemporal control of matter at the nanoscale. By combining the peculiar spatial addressability of DNA origami structures with the switchable mechanical movement of small DNA motifs, we constructed reconfigurable DNA nanochambers as dynamic compartmentalization systems. The reversible extension and contraction of the inner cavity of the structures was used to control the distance-dependent energy transfer between two preloaded fluorophores. Interestingly, single-molecule FRET studies revealed that the kinetics of the process are strongly affected by the choice of the switchable motifs and/or actuator sequences, thus offering a valid method for fine-tuning the dynamic properties of large DNA nanostructures. We envisage that the proposed DNA nanochambers may function as model structures for artificial biomimetic compartments and transport systems.

The protective role of prosaposin and its receptors in the nervous system.

Prosaposin (also known as SGP-1) is an intriguing multifunctional protein that plays roles both intracellularly, as a regulator of lysosomal enzyme function, and extracellularly, as a secreted factor with neuroprotective and glioprotective effects. Following secretion, prosaposin can undergo endocytosis via an interaction with the low-density lipoprotein-related receptor 1 (LRP1). The ability of secreted prosaposin to promote protective effects in the nervous system is known to involve activation of G proteins, and the orphan G protein-coupled receptors GPR37 and GPR37L1 have recently been shown to mediate signaling induced by both prosaposin and a fragment of prosaposin known as prosaptide. In this review, we describe recent advances in our understanding of prosaposin, its receptors and their importance in the nervous system.

Advances in DNA-directed immobilization.

DNA-directed immobilization (DDI) of proteins is a chemically mild and highly efficient method for generating (micro)structured patterns of proteins on surfaces. Twenty years after its initial description, the DDI method has proven its robustness and versatility in numerous applications, ranging from biosensing and biomedical diagnostics, to fundamental studies in biology and medicine on the single-cell level. This review gives a brief summary on technical aspects of the DDI method and illustrates its scope for applications with an emphasis on studies in cell biology.