Fluorescence lifetime imaging microscopy reveals sodium pump dimers in live cells.

The sodium-potassium ATPase (Na/K-ATPase, NKA) establishes ion gradients that facilitate many physiological functions including action potentials and secondary transport processes. NKA comprises a catalytic subunit (alpha) that interacts closely with an essential subunit (beta) and regulatory transmembrane micropeptides called FXYD proteins. In the heart, a key modulatory partner is the FXYD protein phospholemman (PLM, FXYD1), but the stoichiometry of the alpha-beta-PLM regulatory complex is unknown. Here, we used fluorescence lifetime imaging and spectroscopy to investigate the structure, stoichiometry, and affinity of the NKA-regulatory complex. We observed a concentration-dependent binding of the subunits of NKA-PLM regulatory complex, with avid association of the alpha subunit with the essential beta subunit as well as lower affinity alpha-alpha and alpha-PLM interactions. These data provide the first evidence that, in intact live cells, the regulatory complex is composed of two alpha subunits associated with two beta subunits, decorated with two PLM regulatory subunits. Docking and molecular dynamics (MD) simulations generated a structural model of the complex that is consistent with our experimental observations. We propose that alpha-alpha subunit interactions support conformational coupling of the catalytic subunits, which may enhance NKA turnover rate. These observations provide insight into the pathophysiology of heart failure, wherein low NKA expression may be insufficient to support formation of the complete regulatory complex with the stoichiometry (alpha-beta-PLM)2.

Evaluation of a Theory-Based Virtual Counseling Application in Nursing Education.

Effective communication skills in nursing are necessary for high-quality nursing care, but given the decline in nursing students' attitudes and their low self-confidence in effective communication with patients, a participatory and experiential training method is needed. Therefore, a virtual counseling application was developed using artificial intelligence and a three-dimensional avatar to facilitate learning of communication skills. This study aimed to evaluate the effectiveness of this theory-based virtual intervention on nursing students' learning attitudes, communication self-efficacy, and clinical performance. A longitudinal quasi-experimental study was conducted. Ninety-three undergraduate nursing students received virtual patient trainings with four clinical scenarios over 2 years. Data were analyzed using McNemar test and analysis of variance. Virtual patient training improved students' learning attitudes toward communication skills for scenarios involving the pregnant woman (20.4%, P = .03) and depressed patient (17.1%, P = .01) and enhanced perceived self-efficacy for scenarios involving the pregnant woman (22.6%, P = .002) and stressed nursing student (18.3%, P = .002). Students received lower clinical communication scores for pediatric, obstetric, and medical practicums compared with a previous cohort who received no training. Overall, this virtual counseling application can provide a valuable and cost-effective communication learning resource for the nursing curriculum.

Death and dying during COVID-19: The role of health care workers.

A correspondence to an article published in this journal showed that anticipatory grieving and loss during the Corona Virus Disease-19 (COVID-19) pandemic ultimately affects the lives of the family of the bereaved. Advocacy of the health care workers to the patient and their loved ones is necessary. This is where the role of health care workers appears to be important as they, in a sense, serve as a bridge to the dying patient and the grieving family.

The role of religiosity in COVID-19 vaccine hesitancy.

With the surge of COVID-19 cases worldwide, it is essential that vaccination be prioritized to facilitate herd immunity. However, there is vaccine hesitancy reflected in religiosity. This correspondence aims to understand religiosity as a factor that plays a role in vaccination hesitancy. Medical and scientifically sound evidence is influenced by religious beliefs resulting in varied responses toward getting vaccinated such as vaccination hesitancy.

Anticipatory grieving and loss during the COVID-19 pandemic.

Recent correspondence shows that death and burial practices deem significant in understanding the meaning and acceptance of the untimely and unexpected death of a family member afflicted with the coronavirus (COVID-19) disease. These, in turn, raise the need to address the anticipatory grieving process of the family. This paper examines the importance of anticipatory grieving that ultimately affects the lives of the family of the bereaved.

The truth must prevail: citizens' rights to know the truth during the era of COVID-19.

In a recent short report, the necessity of sophisticated practices in gathering records that would facilitate data sharing yields data-driven analysis in time of COVID-19. Consequently, there is a need to present the truth in data analytics in the era of COVID-19. This paper discusses the urgent call for people handling the COVID-19 data to be ethically responsible in their handling, processing, and reporting that impacts the lives of ordinary people especially in this time of pandemic as public health crisis.

TNFα selectively activates the IRE1α/XBP1 endoplasmic reticulum stress pathway in human airway smooth muscle cells.

Airway inflammation is a key aspect of diseases such as asthma. Proinflammatory cytokines such as TNFα mediate the inflammatory response. In various diseases, inflammation leads to endoplasmic reticulum (ER) stress, the accumulation of unfolded proteins, which triggers homeostatic responses to restore normal cellular function. We hypothesized that TNFα triggers ER stress through an increase in reactive oxygen species generation in human airway smooth muscle (hASM) with a downstream effect on mitofusin 2 (Mfn2). In hASM cells isolated from lung specimens incidental to patient surgery, dose- and time-dependent effects of TNFα exposure were assessed. Exposure of hASM to tunicamycin was used as a positive control. Tempol (500 µM) was used as superoxide scavenger. Activation of three ER stress pathways were evaluated by Western blotting: 1) autophosphorylation of inositol-requiring enzyme1 (IRE1α) leading to splicing of X-box binding protein 1 (XBP1); 2) autophosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) leading to phosphorylation of eukaryotic initiation factor 2α; and 3) translocation and cleavage of activating transcription factor 6 (ATF6). We found that exposure of hASM cells to tunicamycin activated all three ER stress pathways. In contrast, TNFα selectively activated the IRE1α/XBP1 pathway in a dose- and time-dependent fashion. Our results indicate that TNFα does not activate the PERK and ATF6 pathways. Exposure of hASM cells to TNFα also decreased Mfn2 protein expression. Concurrent exposure to TNFα and tempol reversed the effect of TNFα on IRE1α phosphorylation and Mfn2 protein expression. Selective activation of the IRE1α/XBP1 pathway in hASM cells after exposure to TNFα may reflect a unique homeostatic role of this pathway in the inflammatory response of hASM cells.

Increased mortality risk associated with serum sodium variations and borderline hypo- and hypernatremia in hospitalized adults.

BACKGROUND: This study aimed to evaluate short-term and long-term mortalities in a cohort of unselected hospitalized patients with serum sodium concentration ([Na+]) variations within and outside of reference range. METHODS: All adult patients admitted to the Mayo Clinic, Rochester, MN, USA from January 2011 to December 2013 (n = 147358) were retrospectively screened. Unique patients admitted during the study period were examined. The main exposure was serum [Na+] variation. Outcome measures were hospital and 1-year all-cause mortalities. RESULTS: A total of 60944 patients, mean age 63 ± 17 years, were studied. On admission, 17% (n = 10066) and 1.4% (n = 852) had hypo- and hypernatremia, respectively. During the hospital stay, 11044 and 4128 developed hypo- and hypernatremia, respectively, accounting for 52.3 and 82.9% of the total hypo- and hypernatremic patients. Serum [Na+] variations of ≥6 mEq/L occurred in 40.6% (n = 24 740) of the 60 944 patients and were significantly associated with hospital and 1-year mortalities after adjusting potential confounders (including demographics, comorbidities, estimated glomerular filtration rate, admission serum [Na+], number of [Na+] measurements and length of hospital stay). Adjusted odds ratios for hospital and 1-year mortalities increased with increasing [Na+] variations in a dose-dependent manner, from 1.47 to 5.48 (all 95% confidence intervals >1.0). Moreover, in fully adjusted models, [Na+] variations (≥6 mEq/L) within the reference range (135-145 mEq/L) or borderline hypo- or hypernatremia (133-137 and 143-147 mEq/L, respectively) compared with 138-142 mEq/L were associated with increased hospital and 1-year mortalities. CONCLUSION: In hospitalized adults, [Na+] fluctuation (≥6 mEq/L) irrespective of admission [Na+] and borderline hypo- or hypernatremia are independent predictors of progressively increasing short- and long-term mortality burdens.

A Virtual Counseling Application Using Artificial Intelligence for Communication Skills Training in Nursing Education: Development Study.

BACKGROUND: The ability of nursing undergraduates to communicate effectively with health care providers, patients, and their family members is crucial to their nursing professions as these can affect patient outcomes. However, the traditional use of didactic lectures for communication skills training is ineffective, and the use of standardized patients is not time- or cost-effective. Given the abilities of virtual patients (VPs) to simulate interactive and authentic clinical scenarios in secured environments with unlimited training attempts, a virtual counseling application is an ideal platform for nursing students to hone their communication skills before their clinical postings. OBJECTIVE: The aim of this study was to develop and test the use of VPs to better prepare nursing undergraduates for communicating with real-life patients, their family members, and other health care professionals during their clinical postings. METHODS: The stages of the creation of VPs included preparation, design, and development, followed by a testing phase before the official implementation. An initial voice chatbot was trained using a natural language processing engine, Google Cloud's Dialogflow, and was later visualized into a three-dimensional (3D) avatar form using Unity 3D. RESULTS: The VPs included four case scenarios that were congruent with the nursing undergraduates' semesters' learning objectives: (1) assessing the pain experienced by a pregnant woman, (2) taking the history of a depressed patient, (3) escalating a bleeding episode of a postoperative patient to a physician, and (4) showing empathy to a stressed-out fellow final-year nursing student. Challenges arose in terms of content development, technological limitations, and expectations management, which can be resolved by contingency planning, open communication, constant program updates, refinement, and training. CONCLUSIONS: The creation of VPs to assist in nursing students' communication skills training may provide authentic learning environments that enhance students' perceived self-efficacy and confidence in effective communication skills. However, given the infancy stage of this project, further refinement and constant enhancements are needed to train the VPs to simulate real-life conversations before the official implementation.

Metadata Correction: A Virtual Counseling Application Using Artificial Intelligence for Communication Skills Training in Nursing Education: Development Study.

[This corrects the article DOI: 10.2196/14658.].

Finding the Right Blend of Technologically Enhanced Learning Environments: Randomized Controlled Study of the Effect of Instructional Sequences on Interprofessional Learning.

BACKGROUND: With the availability and capabilities of varied technologically enhanced learning activities, the blended learning approach has become increasingly popular in interprofessional education. The combined use of different technologically enhanced learning activities has not been fully examined, particularly to determine the effects of instructional sequences for effective learning outcomes. OBJECTIVE: The objective of this study was to investigate whether the instructional sequences of a blended learning approach can improve students' learning outcomes on interprofessional competencies. METHODS: A randomized controlled study was conducted with 40 interprofessional health care teams. These teams undertook three technologically enhanced learning activities-Web-based instruction (WI), virtual reality (VR), and simulation exercise (SE)-after random assignment to three groups based on three different instructional sequences (WI-VR-SE, WI-SE-VR, and SE-WI-VR). Pretests and posttests were conducted to evaluate the students' learning outcomes on interprofessional competencies. RESULTS: A total of 198 participants from the three groups completed the questionnaires. All three groups reported significant improvement in their levels of self-efficacy (P<.05) and attitudes (P<.001) toward interprofessional team care about 1 month after the interprofessional learning activity. Although no significant difference was found (P=.06) between the WI-VR-SE and WI-SE-VR groups in the self-efficacy posttests, participants in the SE-WI-VR group reported significantly lower (P<.05) posttest scores than those in the WI-SE-VR group. The majority of the participants (137/198, 69.1%) selected the instructional sequence "WI-VR-SE" as their top preference. CONCLUSIONS: This study shows that the instructional sequence of a blended learning approach can have a significant impact on students' learning outcomes. The learning of concepts from WI followed by problem-solving activity in the SE was found to be a more effective learning sequence than the reverse sequence. We recommend that future studies focus on scaffolding students' learning when planning instructional sequences for technologically enhanced learning activities within blended learning environments.

Antihypertensive drug associated angioedema: effect modification by race/ethnicity.

PURPOSE: Assess angioedema risk with exposure to angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) compared with beta-blockers, by race/ethnicity. METHODS: New-user cohorts of Medicare beneficiaries 65 years or older initiating ACEI, ARB, or beta-blocker treatment from March 2007 to March 2014 were constructed. Angioedema incidence rates by drug and race/ethnicity were computed for 1-30 and 31-365 days of treatment. Cox proportional hazards regression was used to examine angioedema risk between cohorts. RESULTS: Angioedema incidence rates (per 1000 person years) in beta-blocker users were 1.80 (whites), 4.11 (blacks), 1.89 (Asians), and 2.10 (Hispanics); in ACEI users, 4.03, 23.77, 2.94, and 4.27; and in ARB users, 1.73, 3.11, 1.10, and 1.90, respectively. Incidence rates were significantly higher in the first 30 days of exposure for all drug × race/ethnic groups. Overall, angioedema risk increased among ACEI users (hazard ratio, 2.91; 95% confidence interval, 2.75-3.07) but not ARB users (0.93, 0.85-1.02) versus beta-blocker users. Angioedema risk with ACEIs versus beta-blockers increased more in blacks (6.28, 5.44-7.24) than whites (2.33, 2.19-2.48), Hispanics (2.04, 1.36-3.07), and Asians (1.48, 0.94-2.35). Compared with white beta-blocker users, angioedema risk was increased 2.9-fold in whites, 20.2-fold in blacks, and 2.3-fold in other race/ethnic groups combined during the first 30 days of ACEI exposure. CONCLUSIONS: There was significant effect modification of angioedema risk by race and ACEI use for blacks, but not for other race/ethnicity groups. Angioedema risk was significantly greater in the first 30 days of exposure for all, and highest among blacks.