Best practices for implementation of Kamishibai cards in the healthcare setting to improve nursing-sensitive indicator associated outcomes: An integrative review.

BACKGROUND: Many adverse events are identified as nursing-sensitive indicators (NSIs) and have evidence-based care bundles known to reduce risk of occurrence. Kamishibai cards are a tool from the manufacturing industry used for practice auditing and improvements. Use of Kamishibai cards is believed to be common in the healthcare setting, but true evidence-based guidelines do not yet exist to guide their implementation. AIMS: The aim of this integrative review was to identify best practices around the implementation of Kamishibai cards in the healthcare setting for improvement in NSI-associated outcomes. METHODS: Eleven nurses at three facilities worked through the evidence using the Johns Hopkins Evidence-Based Practice Model. RESULTS: Ten articles were included for this review. Broad themes included direct observation with non-punitive and timely feedback, clearly visualized results, use of evidence-based care bundles, pre-implementation education, and both leadership and frontline-staff involvement. All facilities showed improvement in NSI-associated outcomes after the implementation of K-cards. LINKING ACTION TO ACTION: In health care, K-cards can be implemented and designed with additional focus on the bundles of care they are intended to audit and staff support, but further evidence would better define guidelines around implementation.

K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site.

Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels of the TREK subfamily generate 'leak' currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit. In contrast to other potassium channels, K2P channels use a selectivity filter 'C-type' gate as the principal gating site. Despite recent advances, poor pharmacological profiles of K2P channels limit mechanistic and biological studies. Here we describe a class of small-molecule TREK activators that directly stimulate the C-type gate by acting as molecular wedges that restrict interdomain interface movement behind the selectivity filter. Structures of K2P2.1 (also known as TREK-1) alone and with two selective K2P2.1 (TREK-1) and K2P10.1 (TREK-2) activators-an N-aryl-sulfonamide, ML335, and a thiophene-carboxamide, ML402-define a cryptic binding pocket unlike other ion channel small-molecule binding sites and, together with functional studies, identify a cation-π interaction that controls selectivity. Together, our data reveal a druggable K2P site that stabilizes the C-type gate 'leak mode' and provide direct evidence for K2P selectivity filter gating.

Evaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Rats.

Type 1 diabetes (T1D) is characterized by hyperphagia, hyperglycemia and activation of the hypothalamic-pituitary-adrenal (HPA) axis. We have reported previously that daily leptin injections help to alleviate these symptoms. Therefore, we hypothesized that leptin gene therapy could help to normalize the neuroendocrine dysfunction seen in T1D. Adult male Sprague Dawley rats were injected i.v. with a lentiviral vector containing the leptin gene or green fluorescent protein. Ten days later, they were injected with the vehicle or streptozotocin (STZ). HPA function was assessed by measuring norepinephrine (NE) levels in the paraventricular nucleus (PVN) and serum corticosterone (CS). Treatment with the leptin lentiviral vector (Lepvv) increased leptin and insulin levels in non-diabetic rats, but not in diabetic animals. There was a significant reduction in blood glucose levels in diabetic rats due to Lepvv treatment. Both NE levels in the PVN and serum CS were reduced in diabetic rats treated with Lepvv. Results from this study provide evidence that leptin gene therapy in STZ-induced diabetic rats was able to partially normalize some of the neuroendocrine abnormalities, but studies with higher doses of the Lepvv are needed to develop this into a viable option for treating T1D.

Simulations using telehealth to collaborate with other health-care professionals: effect on pre-licensure nursing students' competencies and amount of collaboration in the clinical setting.

Nursing students must gain experience collaborating with other members of the health-care team. Simulation can provide intra- and interprofessional collaboration experience; however, there can be barriers such as scheduling difficulties. We evaluated multi-patient, standardized patient simulations using telehealth as a strategy to provide baccalaureate nursing students with opportunities to learn and practice intra- and interprofessional collaboration. Forty-four final-semester nursing students participated. Student groups rotated to the simulation laboratory over 12 weeks to participate in two simulations that used telehealth to enable them to communicate patient concerns to other clinicians: a nurse practitioner, respiratory therapists, and social workers. Self-reported collaborative competencies and amount of collaboration in the clinical setting were measured at the start and end of the semester. Satisfaction and self-confidence were measured immediately after each simulation. For collaborative competencies, there was a statistically significant improvement in all item, subscale, and overall scale mean scores. Amount of clinical collaboration significantly improved, with the amount who indicated they never reported a patient concern to another professional decreasing from 39.5% to 6.8%. Findings also revealed a high level of student satisfaction and self-confidence following the simulations. Using telehealth to collaborate during simulations is a promising strategy to prepare nursing students for practice by improving collaborative competencies and encouraging more collaboration in the clinical setting.

Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains.

K(2P)2.1 (TREK-1) is a polymodal two-pore domain leak potassium channel that responds to external pH, GPCR-mediated phosphorylation signals, and temperature through the action of distinct sensors within the channel. How the various intracellular and extracellular sensory elements control channel function remains unresolved. Here, we show that the K(2P)2.1 (TREK-1) intracellular C-terminal tail (Ct), a major sensory element of the channel, perceives metabolic and thermal commands and relays them to the extracellular C-type gate through transmembrane helix M4 and pore helix 1. By decoupling Ct from the pore-forming core, we further demonstrate that Ct is the primary heat-sensing element of the channel, whereas, in contrast, the pore domain lacks robust temperature sensitivity. Together, our findings outline a mechanism for signal transduction within K(2P)2.1 (TREK-1) in which there is a clear crosstalk between the C-type gate and intracellular Ct domain. In addition, our findings support the general notion of the existence of modular temperature-sensing domains in temperature-sensitive ion channels. This marked distinction between gating and sensory elements suggests a general design principle that may underlie the function of a variety of temperature-sensitive channels.

Multiple modalities converge on a common gate to control K2P channel function.

Members of the K(2P) potassium channel family regulate neuronal excitability and are implicated in pain, anaesthetic responses, thermosensation, neuroprotection, and mood. Unlike other potassium channels, K(2P)s are gated by remarkably diverse stimuli that include chemical, thermal, and mechanical modalities. It has remained unclear whether the various gating inputs act through separate or common channel elements. Here, we show that protons, heat, and pressure affect activity of the prototypical, polymodal K(2P), K(2P)2.1 (KCNK2/TREK-1), at a common molecular gate that comprises elements of the pore-forming segments and the N-terminal end of the M4 transmembrane segment. We further demonstrate that the M4 gating element is conserved among K(2P)s and is employed regardless of whether the gating stimuli are inhibitory or activating. Our results define a unique gating mechanism shared by K(2P) family members and suggest that their diverse sensory properties are achieved by coupling different molecular sensors to a conserved core gating apparatus.

Assessing Evidence-Based Practice Knowledge, Self-Efficacy, and Use Among Respiratory Therapists.

BACKGROUND: Evidence-based practice is at the forefront of providing quality patient care by using the best available evidence and clinical expertise, while also considering patient needs and preferences for clinical decisions. However, evidence-based practice may not be consistently used even when the evidence supports the therapy. The purpose of this study was to assess the factors associated with the use of evidence-based practice among respiratory therapy faculty teaching in a large community college system and post-professional students enrolled in a university-based, respiratory therapy baccalaureate degree-advancement program. METHODS: A non-probability, descriptive survey research design was used to develop and administer an online questionnaire. RESULTS: All respondents demonstrated sufficient knowledge and understanding of introductory concepts of evidence-based practice but knowledge of specific components of the evidence-based practice process was not as strong. Self-efficacy in knowledge and the use of evidence-based practice among faculty and degree-advancement students varied. Faculty and students rated their self-efficacy high in assessing patients' needs, values, and treatment preferences but ratings were lower for using the PICO (patient/population/problem, intervention, comparison, outcome) technique and interpreting common statistical tests. Students viewed their previous evidence-based practice learning experiences more favorably compared with faculty (P = .008). Faculty and students searched and read the research literature more often compared with critically appraising and using the research literature. Logistic regression analysis indicated no statistically significant relationship of knowledge, self-efficacy, and learning experiences to the use of evidence-based practice among respiratory therapy students, Χ 2 (4, N = 54) = 7.73; P = .10. CONCLUSIONS: Analysis of the results suggested that respiratory therapy faculty and students were knowledgeable and confident with regard to evidence-based practice but their use of evidence-based practice in clinical decisions was limited. Although the evidence-based practice knowledge, self-efficacy, and learning experiences had minimal influence on the use of evidence-based practice, the results of the study provide a foundation for future research.

Factor IX complex for the treatment of severe bleeding after cardiac surgery.

BACKGROUND: Previous reports have been published on the use of recombinant Factor VIIa for intractable bleeding after cardiac surgery; however, there is limited information on the use of Factor IX Complex in this population. METHODS: A retrospective cohort study of adult patients who underwent cardiac surgery and experienced severe postoperative bleeding, defined as a mean chest tube output ≥300 mL/h. Primary outcomes were changes in chest tube output and blood product usage pre- and post-Factor IX Complex administration. RESULTS: Eleven patients received Factor IX Complex for severe postoperative bleeding. The mean dose of Factor IX Complex was 35 (13-52) units/kg. Chest tube output was significantly reduced after Factor IX Complex administration (mean pre-Factor IX Complex 381 ± 49 mL/h, mean post-Factor IX Complex 151 ± 38 mL/h; P = 0.003). Blood product usage decreased after Factor IX Complex but was not statistically significant (mean pre-Factor IX Complex 373 ± 81 mL/h, mean post-Factor IX Complex 212 ± 48 mL/h; P = 0.669). Adverse events included 1 pulmonary embolism (postoperative day 43) and 2 episodes of acute renal failure requiring dialysis (postoperative days 2 and 5). CONCLUSIONS: In this small group of patients, Factor IX Complex effectively controlled severe bleeding after cardiac surgery preventing the need for re-exploration.

Impact of a clinical pharmacy admission medication reconciliation program on medication errors in "high-risk" patients.

BACKGROUND: Medication errors are common upon hospital admission. Clinical pharmacist involvement in medication reconciliation is effective in identifying and rectifying medication errors. However, data is lacking on the economic impact, time requirements, and severity of errors resolved by clinical pharmacists. OBJECTIVE: To determine the incidence of unintended admission medication discrepancies resolved by clinical pharmacists. Secondary objectives were to determine the type of discrepancies, potential severity, proximal cause, and economic impact of this clinical pharmacy program. METHODS: This was a single-center, prospective, observational study conducted at a major teaching medical institution. Following institutional review board approval, data collection was conducted over a 4-week period (August 22, 2011, to September 16, 2011). Descriptive statistical methods were performed for all data analyses. RESULTS: A total of 517 patients involving 5006 medications were included in this study. More than 25% (n = 132) of patients had at least 1 error associated with a medication ordered on hospital admission. Pharmacists resolved a total of 467 admission medication errors (3.5 ± 2.3 errors/patient). The most common type of medication error resolved was medication omission (79.6%). In regard to severity, 46% of medication errors were considered significant or serious. Overall, the mean total time was 44.4 ± 21.8 minutes per medication reconciliation. This clinical pharmacy program was estimated to carry a net present value of $5.7 million over 5 years. CONCLUSION: Clinical pharmacist involvement within a multidisciplinary health care team during the admission medication reconciliation process demonstrated a significant improvement in patient safety and an economic benefit.

Tonic Meningeal Interleukin-10 Upregulates Delta Opioid Receptor to Prevent Relapse to Pain.

Chronic pain often alternates between transient remission and relapse of severe pain. While most research on chronic pain has focused on mechanisms maintaining pain, there is a critical unmet need to understand what prevents pain from re-emerging in those who recover from acute pain. We found that interleukin (IL)-10, a pain resolving cytokine, is persistently produced by resident macrophages in the spinal meninges during remission from pain. IL-10 upregulated expression and analgesic activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of IL-10 signaling or δOR triggered relapse to pain in both sexes. These data challenge the widespread assumption that remission of pain is simply a return to the naïve state before pain was induced. Instead, our findings strongly suggest a novel concept that: remission is a state of lasting pain vulnerability that results from a long-lasting neuroimmune interactions in the nociceptive system.

Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice.

Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.

Structural insight into KCNQ (Kv7) channel assembly and channelopathy.

Kv7.x (KCNQ) voltage-gated potassium channels form the cardiac and auditory I(Ks) current and the neuronal M-current. The five Kv7 subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain Tail. Here, we present the high-resolution structure of the Kv7.4 A-domain Tail together with biochemical experiments that show that the domain is a self-assembling, parallel, four-stranded coiled coil. Structural analysis and biochemical studies indicate conservation of the coiled coil in all Kv7 subtypes and that a limited set of interactions encode assembly specificity determinants. Kv7 mutations have prominent roles in arrhythmias, deafness, and epilepsy. The structure together with biochemical data indicate that A-domain Tail arrhythmia mutations cluster on the solvent-accessible surface of the subunit interface at a likely site of action for modulatory proteins. Together, the data provide a framework for understanding Kv7 assembly specificity and the molecular basis of a distinct set of Kv7 channelopathies.

Expression and clinical significance of the transforming growth factor-ß signalling pathway in endometrial cancer.

AIMS: To evaluate the components of the transforming growth factor (TGF)-ß-Smad signalling pathway in human endometrial cancer (EC). METHODS AND RESULTS: TGF-ß1, TGF-ß receptor type I, TGF-ß receptor type II, Smad2, Smad3, Smad4, Skil and Disabled-2 (DAB2) mRNA levels were determined by reverse transcriptase polymerase chain reaction on EC cell lines and in 70 EC tissues. Immunohistochemistry for Skil and DAB2 antibodies was performed on 362 EC cases. Decreased mRNA levels of all eight components of the TGF-ß pathway tested were found in the majority of 70 cases. For DAB2, the mRNA level was correlated with protein expression level (P = 0.04). The Skil mRNA level was associated with tumour stage (P = 0.03), and the Smad2/3/4 mRNA level with tumour grade (P = 0.03, P = 0.02, and P = 0.00, respectively). The Smad4 mRNA level was also associated with tumour size (P = 0.05), subtype (P = 0.04), and disease-free survival (DFS) (P = 0.05). The TGF-ß1 mRNA level was associated with DFS (P = 0.04). Finally, tumours with positive Skil protein expression had a shorter recurrence time, whereas, those with positive DAB2 protein expression had a longer recurrence time. CONCLUSIONS: Down-regulation of the TGF-ß-Smad signalling pathway might be responsible for the pathogenesis of human EC, and some of its components appeared to be prognostic factors. Exploration of future therapy targeting the TGF-ß-Smad pathway is warranted in EC.

Nursing Students Behind Bars.

BACKGROUND: With a large incarcerated patient population in the United States, there is a unique potential for clinical learning for undergraduate nursing students with this population. METHOD: The Virginia Commonwealth University (VCU) School of Nursing and VCU Health System have created a unique partnership in which baccalaureate nursing students complete their first clinical rotation on VCU Health System's Secure Care Unit (SCU). At the conclusion of their semester, baccalaureate students assigned to the SCU for the fundamentals clinical were asked to provide feedback on their experiences. RESULTS: Both challenges and positive outcomes were identified by students who completed their first clinical rotation providing care to this unique population. CONCLUSION: The formation of this relationship between the VCU School of Nursing and the VCU Health System's SCU is helping to meet patient, student, and clinical unit needs and also making a positive impact on the stakeholders involved. [J Nurs Educ. 2021;60(8):470-471.].

Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.

Voltage-gated calcium channels (Ca(V)s) govern muscle contraction, hormone and neurotransmitter release, neuronal migration, activation of calcium-dependent signalling cascades, and synaptic input integration. An essential Ca(V) intracellular protein, the beta-subunit (Ca(V)beta), binds a conserved domain (the alpha-interaction domain, AID) between transmembrane domains I and II of the pore-forming alpha(1) subunit and profoundly affects multiple channel properties such as voltage-dependent activation, inactivation rates, G-protein modulation, drug sensitivity and cell surface expression. Here, we report the high-resolution crystal structures of the Ca(V)beta2a conserved core, alone and in complex with the AID. Previous work suggested that a conserved region, the beta-interaction domain (BID), formed the AID-binding site; however, this region is largely buried in the Ca(V)beta core and is unavailable for protein-protein interactions. The structure of the AID-Ca(V)beta2a complex shows instead that Ca(V)beta2a engages the AID through an extensive, conserved hydrophobic cleft (named the alpha-binding pocket, ABP). The ABP-AID interaction positions one end of the Ca(V)beta near the intracellular end of a pore-lining segment, called IS6, that has a critical role in Ca(V) inactivation. Together, these data suggest that Ca(V)betas influence Ca(V) gating by direct modulation of IS6 movement within the channel pore.

Alanine-scanning mutagenesis defines a conserved energetic hotspot in the CaValpha1 AID-CaVbeta interaction site that is critical for channel modulation.

Voltage-gated calcium channels (CaVs) are large, multisubunit complexes that control cellular calcium entry. CaV pore-forming (CaValpha1) and cytoplasmic (CaVbeta) subunits associate through a high-affinity interaction between the CaValpha1 alpha interaction domain (AID) and CaVbeta alpha binding pocket (ABP). Here we analyze AID-ABP interaction thermodynamics using isothermal titration calorimetry. We find that commensurate with their strong sequence similarity, all CaV1 and CaV2 AID peptides bind CaVbeta with similar nanomolar affinities. Although the AID-ABP interface encompasses 24 side chains, alanine-scanning mutagenesis reveals that the binding energy is focused in two complementary hotspots comprising four deeply conserved residues. Electrophysiological experiments show that hotspot interaction disruption prevents trafficking and functional modulation of CaV1.2 by CaVbeta. Together, the data support the primacy of the AID-ABP interface for CaValpha1-CaVbeta association, underscore the idea that hotspots dominate protein-protein interaction affinities, and uncover a target for strategies to control cellular excitability by blocking CaValpha1-CaVbeta complex formation.

Ventilator Graphics: Scalars, Loops, & Secondary Measures.

Ventilator graphic monitoring is common in ICUs. The graphic information provides clinicians with immediate clues regarding patient-ventilator interaction and ventilator function. These display tools are aimed at reducing complications associated with mechanical ventilation, such as patient-ventilator asynchrony. It is also useful to assess respiratory mechanics in mechanically ventilated patients using both scalar and plot displays on the ventilator. Additional information can be gained by observing secondary ventilator measures including stress index, inflection points, and work of breathing. Ventilator graphics impact mechanical ventilation management through optimizing effectiveness of patient care and enhancing promptness of clinician response. Despite being a valuable asset in providing high-quality patient care, many bedside clinicians do not have a thorough understanding of ventilator graphics. Mastery of ventilator graphics interpretation is key in managing patients who are receiving ventilatory support.

"Healthy"/"Unhealthy" Food Brands Influence Health, Calorie, and Price Ratings of Food.

OBJECTIVE: To assess the effect of healthy or unhealthy food brands on consumer ratings of a food's perceived healthfulness, caloric content, and estimated price. METHODS: Using a crossover design, 35 adults aged 18-25 years scored a variety of healthy and unhealthy foods paired with "healthy" or "unhealthy" brands or with no brand present, on their healthfulness, caloric content, and estimated price. For each outcome measure, ANOVA was used to evaluate the effect of brand condition on healthy and unhealthy foods. RESULTS: Pairing an unhealthy food with a "healthy brand" led to increased ratings of healthfulness (P < .001), decreased estimates of caloric content (P < .001), and increased price (P < .001). Pairing a healthy food with an "unhealthy brand" led to decreased ratings of healthfulness (P < .001), increased estimates of caloric content (P < .001), and decreased price (P < .001). CONCLUSIONS AND IMPLICATIONS: These findings extend previous research showing that brands may influence perceptions of food products. Future studies are needed to understand the implications of pairing healthy foods with "unhealthy brands" on actual food intake.

Baccalaureate nursing students' experiences with multi-patient, standardized patient simulations using telehealth to collaborate.

BACKGROUND: Nurse faculty must utilize teaching strategies that promote student achievement of essential competencies, and simulation can provide experiential learning to help prepare students for professional practice. PURPOSE: The purpose of this phenomenological qualitative study was to explore baccalaureate nursing students' experiences with multi-patient, standardized patient simulations that used telehealth to provide opportunities to learn and practice intra- and interprofessional collaboration. Student perceptions of their ability to utilize lessons from the simulations in clinical practice were also examined. METHODS: Focus group interviews were conducted with 27 final-semester baccalaureate nursing students after they had participated in two telehealth-enhanced simulations. RESULTS: Analysis revealed five themes: Anxiety due to lack of experience, Improved clinical reasoning, Real world practice, How to communicate effectively, and Application to clinical practice. CONCLUSION: The use of telehealth helped overcome barriers to implementing collaborative simulations and provided students with experiential learning that addressed essential competencies for safe and effective professional nursing practice.

MYC DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score.

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10-4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.