Exploring helix structures of γ-peptides based on 2-(aminomethyl)cyclopentanecarboxylic acid.

Conformational search and density functional theory calculations were performed to explore the preferences of helical structures for chiro-specific oligo-γ-peptides of 2-(aminomethyl)cyclopentanecarboxylic acid (γAmc5) with a cyclopentyl constraint on the Cα-Cß bond in solution. The dimer and tetramer of γAmc5 (1) with homochiral (1S, 2S) configurations exhibited a strong preference for the 9-membered helix foldamer in solution, except for the tetramer in water. However, the oligomers of γAmc5 (1) longer than tetramer preferentially adopted a right-handed (P)-2.614-helix (H1-14) as the peptide sequence becomes longer and as solvent polarity increases. The high stabilities for H1-14 foldamers of γAmc5 (1) in solution were ascribed to the favored solvation free energies. The calculated mean backbone torsion angles for H1-14 helix foldamers of γAmc5 (1) were similar to those calculated for oligomers of other γ-residues with cyclopentane or cyclohexane rings. However, the substitution of cyclopentane constraints on the Cα-Cß bond of the γAmc5 (1) residue resulted in different conformational preferences and/or handedness of helix foldamers. In particular, the pyrrolidine-substituted analogs of the H1-14 foldamers of γAmc5 (1) with adjacent amine diads substituted at a proximal distance are expected to be potential catalysts for the crossed aldol condensation in nonpolar and polar solvents.

Job satisfaction and moral distress of nurses working as physician assistants: focusing on moderating role of moral distress in effects of professional identity and work environment on job satisfaction.

BACKGROUND: Physician assistant was created in response to a shortage of physicians. However, this profession is not officially recognized in Korea. Many nurses are working as physician assistants. Their job satisfaction was low due to role conflict. Job satisfaction plays a major role in providing high quality nursing. This study aimed to investigate effects of work environment and professional identity on job satisfaction and identify the mediating role of moral distress in such effects. METHODS: Participants were 112 nurses working as physician assistants. They were recruited from three General Hospitals. A questionnaire scale was used to collect data. Data were analyzed using frequency, descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation, and Macro Model 4 with SPSS Statistics. RESULTS: Job satisfaction of nurses working as physician assistants had a score of 3.08 out of 5. It showed significant associations with work environment and professional identity. Moral distress had a partial mediating role in relationships of job satisfaction with work environment and professional identity. CONCLUSION: Many nurses are working as physician assistants, although physician assistant as a profession is not officially recognized in Korea. Nurses working as physician assistants experience confusion about their professional identity and moral distress. For better nursing outcomes, physician assistant policy should be improved, and various strategies should be provided to improve their job satisfaction.

What topics are women interested in during pregnancy: exploring the role of social media as informational and emotional support.

BACKGROUND: Social media plays an important role as a source for obtaining or sharing health information. It is frequently used as a resource by pregnant women who seek information and emotional support regarding their physical and role changes. To provide high-quality support for pregnant women, it is important to determine what topics they want information on from social media during their pregnancy, and what effects they expect from each topic. This study investigates what topics pregnant women are interested in according to their stage of pregnancy and need for informational or emotional support from each topic of interest. METHODS: An online survey was conducted with 302 pregnant Korean women. The survey questionnaires included information sources and experience of social media. Along with the questionnaires, they were asked to describe three to ten health topics that they were most interested in in the last two weeks. RESULTS: Social media (72.85%) and search engines (72.85%) were found to be most frequently used for pregnancy-related health information. The topics of interest slightly differed by stage, but mainly postpartum care, pregnancy symptoms, and daily life issues ranked high. Mood related topics appeared frequently among women in their first trimester or post-partum stage of pregnancy. Informational support was mostly needed for daily life issues, and emotional support needs centered mostly around stories about family and mood during pregnancy. CONCLUSIONS: Pregnant women have different needs for informational or emotional support, depending on their stage of pregnancy and their topics of interest. Therefore, social media support should be delivered with varying content and platforms tailored to women's needs at each trimester.

Animal-Assisted Therapy as an Intervention for Older Adults: A Systematic Review and Meta-Analysis to Guide Evidence-Based Practice.

BACKGROUND: Animal-assisted therapy (AAT) can ameliorate diverse health problems in older adults. However, applications of AAT have been limited because of the lack of intervention guidelines for older adults. AIMS: This study aimed to explore applications of AAT to older adults, analyze its health effects, and provide evidence for future interventions. METHODS: A systematic review and meta-analysis were conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Data were analyzed based on both a narrative synthesis and a meta-analysis specifically for depression. RESULTS: A total of 47 studies were selected for analysis. About 45% focused on older adults with diseases such as dementia, and 57.4% selected dog(s) as an intervention animal. About 34.0% delivered interventions once a week, and the behavioral outcome domain was the most frequently investigated. The meta-analysis showed that the effect sizes of the AAT group were -1.310 (95% CI [-1.900, -.721]). LINKING EVIDENCE TO ACTION: This review provides evidence for AAT as an intervention in the physiological, psychosocial, cognitive, and behavioral domains of older adults. When planning interventions for older adults, nurses should consider intended health outcomes, appropriate therapeutic animals, and the consequent intervention contents.

Relationships between determinants of adjuvant endocrine therapy adherence in breast cancer.

BACKGROUND: Interventions that promote adjuvant endocrine therapy (AET) adherence are critical to improve breast cancer survival. The development of interventions would benefit from a better understanding of the reasons for adherence and the causal relationships of determinants using theoretical or model approaches. The aim of the present study was to identify reasons for AET adherence in breast cancer patients with sequential relationships and inter-relationships. METHODS: A total of 210 participants with estrogen receptor positive breast cancer who received AET completed a questionnaire assessing demographic/medical, psychological, and endocrine therapy (ET)-specific factors. A descriptive analysis was performed to identify meaningful variables. Selected variables were subjected to hierarchical regression and path analyses. The path model was tested and modified based on the research framework and the results of regression weights and model fit. RESULTS: Analysis of sequential effects showed that ET-specific factors contributed the largest proportion of variance (13.4%) to predict AET adherence, followed by psychological factors (4.6%) and demographic/medical factors (3.1%). Analysis of inter-relationships showed that demographic/medical factors such as AET regimen type and cancer stage have direct effects on AET adherence, whereas psychological factors contribute indirectly through the mediating effects of ET-specific factors. CONCLUSION: Assessments and interventions that encompass the patient's medication beliefs, self-efficacy, and depression are needed to promote AET adherence.

Remote Stereoinductive Intramolecular Nitrile Oxide Cycloaddition: Asymmetric Total Synthesis and Structure Revision of (-)-11ß-Hydroxycurvularin.

The first total synthesis and structure revision of (-)-11ß-hydroxycurvularin (1b), a macrolide possessing a ß-hydroxyketone moiety, were accomplished. The ß-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5-remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition.

Discovery of indirubin derivatives as new class of DRAK2 inhibitors from high throughput screening.

DRAK2 is a serine/threonine kinase belonging to the death-associated protein kinase (DAPK) family and has emerged as a promising drug target for the treatment of autoimmune diseases and cancers. To identify small molecule inhibitors for DRAK2, we performed a high throughput screening campaign using in-house chemical library and identified indirubin-3'-monoximes as novel class of DRAK2 inhibitors. Among the compounds tested, compound 16 exhibited the most potent inhibitory activity against DRAK2 (IC50=0.003µM). We also propose that compound 16 may bind to the ATP-binding site of the enzyme based on enzyme kinetics and molecular docking studies.

Discovery of novel tetrahydroisoquinoline-containing pyrimidines as ALK inhibitors.

Exploration of the two-position side chain of pyrimidine in LDK378 with tetrahydroisoquinolines (THIQs) led to discovery of 8 and 17 as highly potent ALK inhibitors. THIQs 8 and 17 showed encouraging in vitro and in vivo xenograft efficacies, comparable with those of LDK378. Although THIQ analogs (8a-o and 17a-i) prepared were not as active as their parent compounds, both 8 and 17 have significant inhibitory activities against various ALK mutant enzymes including G1202R, indicating that this series of compounds could be further optimized as useful ALK inhibitors overcoming the resistance issues found from crizotinib and LDK378.

Praeruptorin A inhibits in vitro migration of preosteoclasts and in vivo bone erosion, possibly due to its potential to target calmodulin.

Excessive activity and/or increased number of osteoclasts lead to bone resorption-related disorders. Here, we investigated the potential of praeruptorin A to inhibit migration/fusion of preosteoclasts in vitro and bone erosion in vivo. Praeruptorin A inhibited the RANKL-induced migration/fusion of preosteoclasts accompanied by the nuclear translocation of NFATc1, a master regulator of osteoclast differentiation. Antimigration/fusion activity of praeruptorin A was also confirmed by evaluating the mRNA expression of fusion-mediating molecules. In silico binding studies and several biochemical assays further revealed the potential of praeruptorin A to bind with Ca(2+)/calmodulin and inhibit its downstream signaling pathways, including the Ca(2+)/calmodulin-CaMKIV-CREB and Ca(2+)/calmodulin-calcineurin signaling axis responsible for controlling NFATc1. In vivo application of praeruptorin A significantly reduced lipopolysaccharide-induced bone erosion, indicating its possible use to treat bone resorption-related disorders. In conclusion, praeruptorin A has the potential to inhibit migration/fusion of preosteoclasts in vitro and bone erosion in vivo by targeting calmodulin and inhibiting the Ca(2+)/calmodulin-CaMKIV-CREB-NFATc1 and/or Ca(2+)/calmodulin-calcineurin-NFATc1 signaling axis.

A novel assessment of nefazodone-induced hERG inhibition by electrophysiological and stereochemical method.

Nefazodone was used widely as an antidepressant until it was withdrawn from the U.S. market in 2004 due to hepatotoxicity. We have investigated methods to predict various toxic effects of drug candidates to reduce the failure rate of drug discovery. An electrophysiological method was used to assess the cardiotoxicity of drug candidates. Small molecules, including withdrawn drugs, were evaluated using a patch-clamp method to establish a database of hERG inhibition. Nefazodone inhibited hERG channel activity in our system. However, nefazodone-induced hERG inhibition indicated only a theoretical risk of cardiotoxicity. Nefazodone inhibited the hERG channel in a concentration-dependent manner with an IC50 of 45.3nM in HEK-293 cells. Nefazodone accelerated both the recovery from inactivation and its onset. Nefazodone also accelerated steady-state inactivation, although it did not modify the voltage-dependent character. Alanine mutants of hERG S6 and pore region residues were used to identify the nefazodone-binding site on hERG. The hERG S6 point mutants Y652A and F656A largely abolished the inhibition by nefazodone. The pore region mutant S624A mildly reduced the inhibition by nefazodone but T623A had little effect. A docking study showed that the aromatic rings of nefazodone interact with Y652 and F656 via π-π interactions, while an amine interacted with the S624 residue in the pore region. In conclusion, Y652 and F656 in the S6 domain play critical roles in nefazodone binding.

Prognosis and Adjusting Factors in Elderly Patients With Triple-Negative Breast Cancer: Comparing With Young and Middle Age Groups.

PURPOSE: Proper breast cancer screening and treatment should be considered in the elderly population; however, some tend to be less proactive. Our study aimed to investigate the impact of old age on treatment and prognosis in triple-negative breast cancer (TNBC). METHOD: The study included patients with primary TNBC stage I-III diagnosed from 2002 to 2019 in single institution and retrospectively analyzed. We defined young (< 40 years), middle and old (> 70 years) groups. Clinicopathological factors, treatment, and prognosis were analyzed according to age group of TNBC patients. RESULT: TNBC patients aged 70 and above were 3.3 times more likely (P = .019) to have lymph node metastasis at the time of diagnosis compared to younger patients, but were found to be 0.24 times less likely to receive chemotherapy. (P = .003) Old TNBC patients have an expected likelihood 2.2 times higher of undergoing mastectomy rather than breast-conserving surgery. (P = .042) The 5-year prognosis is poorer in young and old group. (61%, 86%, and 65% in young, middle, and old groups). (P < .001). In subanalysis, old group of stages I and II received fewer chemotherapy compared to youngers (P < .05), but not in stage III. In Cox regression analysis, age and stage had significant impact on prognosis (hazard ratio 2-3), but treatment factors did not. However, in stratified analysis of adjuvant therapy and stage, prognosis of Old TNBC patients in stage II was improved when they underwent neo or adjuvant chemotherapy. CONCLUSION: TNBC presents challenges in older patients, who receive less aggressive treatment and have poorer outcomes. The primary cause of poor prognosis in old TNBC patients is the high disease stage at diagnosis, underscoring the need for promotion and education on early screening. Additionally, it is suggested that a more proactive approach to adjuvant chemotherapy is necessary for stage II old TNBC patients.

Validation of a Korean version of mobile app rating scale (MARS) for apps targeting disease management.

The mobile app rating scale (MARS) is a widely used instrument for evaluating smartphone app quality. We aimed to examine the reliability and validity of the Korean version of MARS (MARS-K). Two independent raters performed the assessment using the translated 23-item questionnaire. We applied intraclass correlation coefficient analysis (ICC) to examine inter-rater reliability, Omega, and item-total correlation for internal consistency, and Pearson's r for test-retest reliability and correlation between subscales and the total score of MARS-K. Most items showed moderate to good ICC (0.447-1.000). The MARS-K showed excellent internal consistency and all subscales exceeded the acceptable level of omega. Results indicated MARS-K to be a valid and reliable instrument for evaluating disease management apps offered in the Korean app store. However, upgrades are recommended to further improve MARS-K's rating accuracy and reliability.

Simulation Education Incorporating Academic Electronic Medical Records for Undergraduate Nursing Students: A Pilot Study.

OBJECTIVES: Academic electronic medical records (AEMRs) can be utilized for a variety of educational programs that can enhance nursing students' nursing informatics and clinical reasoning competencies. This study aimed to identify the applicability and effectiveness of simulation education incorporating AEMRs. METHODS: We developed simulation education scenarios incorporating AEMRs and evaluated them with 76 third- and fourth-year nursing students from five nursing schools using a mixed-methods design. We incorporated three simulation case scenarios involving preeclampsia, diabetes mellitus, and myocardial infarction into the AEMRs. After the simulation education, participants' feedback on the usability of the AEMR system and their self-efficacy for AEMR utilization were collected via self-reported surveys. Subsequently, the simulation education incorporating AEMRs was evaluated through a focus group interview. The survey data were examined using descriptive statistics, and thematic analysis was done for the focus group interview data. RESULTS: The average mean scores for the AEMR system's usability and participants' self-efficacy for AEMR utilization were 5.36 of 7 and 3.96 of 5, respectively. According to the focus group interviews, the participants were satisfied with the simulation education incorporating AEMRs and recognized their confidence in AEMR utilization. In addition, participants addressed challenges to simulation education incorporating AEMRs, including the need for pre-education and AEMR utilization difficulties. CONCLUSIONS: Nursing students were satisfied with and recognized the value of simulation education incorporating AEMRs. Although the actual application of simulation education incorporating AEMRs remains challenging, further research can help develop and implement this approach for nursing students.

Ontology-Based Natural Language Processing of Social Media Data in the Assessment of Health Information Sought During Pregnancy.

This study analyzed collected social media data from South Korea containing keywords related to "pregnancy" using ontology-based natural language processing. Of the 504,725 documents, those containing concepts related to "maternal emotion" were the most frequent, followed by "family support". Social media were used as a means of exchanging information and expressing emotions.

Systematic Review of Prediction Models for Preterm Birth Using CHARMS.

OBJECTIVE: This study sought to evaluate prediction models for preterm birth (PTB) and to explore predictors frequently used in PTB prediction models. METHODS: A systematic review was conducted. We selected studies according to the PRISMA, classified studies according to TRIPOD, appraised studies according to the PROBAST, and extracted and synthesized the data narratively according to the CHARMS. We classified the predictors in the models into socio-economic factors with demographic, psychosocial, biomedical, and health behavioral factors. RESULTS: Twenty-one studies with 27 prediction models were selected for the analysis. Only 16 models (59.3%) defined PTB outcomes as 37 weeks or less, and seven models (25.9%) defined PTB as 32 weeks or less. The PTB rates varied according to whether high-risk pregnant women were included and according to the outcome definition used. The most frequently included predictors were age (among demographic factors), height, weight, body mass index, and chronic disease (among biomedical factors), and smoking (among behavioral factors). CONCLUSION: When using the PTB prediction model, one must pay attention to the outcome definition and inclusion criteria to select a model that fits the case. Many studies use the sub-categories of PTB; however, some of these sub-categories are not correctly indicated, and they can be misunderstood as PTB (≤ 37 weeks). To develop further PTB prediction models, it is necessary to set the target population and identify the outcomes to predict.

Ionic interactions for substituted MCH1R inhibitors studied by pK(a) values.

MCH1R inhibitors with the quinoline moiety having the aromatic amine and aliphatic amine chain were selected, and then the effect of substituents of the quinoline ring on the ionic interaction were studied by calculating pK(a) values for these amines at the B3LYP/6-311++G(d,p)//B3LYP/6-31+G(d) level in the gas phase and in water. For substituent with C, N, O, and S atoms next to the quinoline ring, respectively, the pK(a) values of aromatic amines are estimated to be 8.98, 12.19, 4.64, and 4.33 and those of the aliphatic amines are 12.65, 10.82, 9.94, and 11.55, respectively.

An Ontology for Assessing Health Information Needed During Pregnancy.

In this study we developed an ontology for accessing online health information related to pregnancy. Social media data and the categories in the literature on pregnancy information were used to collect terms for identifying class and class hierarchy. The developed ontology included 241 classes and 788 synonyms, with six superclasses. This ontology can be used to provide appropriate information based on a needs assessment.

The rate enhancement for prolyl cis-to-trans isomerization of cyclic CPFC peptide is caused by an increase in the vibrational entropy of the transition state.

The conformational preferences and prolyl cis-trans isomerization of oxidized and reduced Ac-Cys-Pro-Phe-Cys-NH2 (CPFC peptides) have been carried out using the ab initio HF/6-31+G(d) and hybrid density functional B3LYP/6-311++G(d,p) levels of theory. The most preferred conformations of oxidized and reduced CPFC peptides with the trans prolyl peptide bond have a type-I beta-turn for the Pro-Phe sequence in common. In particular, the transition states for both forms are stabilized by the intramolecular hydrogen bonds between the prolyl nitrogen and the N-H group of the Phe3 residue. The rotational barrier DeltaGct to the cis-to-trans isomerization for the oxidized CPFC peptide is calculated to be 19.37 kcal/mol at the B3LYP/6-311++G(d,p)//HF/6-31+G(d) level of theory, which is lower by 0.88 kcal/mol than that of the reduced CPFC peptide. This may indicate that the rate constant kc-->t of the prolyl cis-to-trans isomerization for the oxidized form is about 4 times larger than that of the reduced form, which is reasonably consistent with the value deduced from NMR experiments. In particular, the increase in vibrational entropy for the transition state of the oxidized form over that of the reduced form contributes to enhance the rate constant for the prolyl cis-to-trans isomerization of the oxidized form.

Conformational preferences and pKa value of cysteine residue.

The conformational preferences of the Cys dipeptides with thiol and thiolate groups (Ac-Cys-NHMe and Ac-Cys (-)-NHMe, respectively) and the apparent (i.e., macroscopic) p K a value of the Cys dipeptide have been studied at the hybrid density functional B3LYP/6-311++G(d,p)//B3LYP/6-31+G(d) level with the conductor-like polarizable continuum model in the gas phase and in water. The hydrogen bonds and/or favorable interactions between the backbone and the thiol group of the side chain resulted in the different conformational preferences of the Cys and Cys (-) dipeptides from those of the Ala dipeptide in the gas phase and in water, although the preferred conformations of the Cys dipeptide are in part similar to those of the Ala dipeptide. In particular, the interactions between the thiolate group and the backbone amide groups appear to play a role in stabilizing the alpha- or 3 10-helical conformations for the Cys (-) dipeptide in the gas phase and in water. The p K a value of the Cys residue is estimated to be 8.58 at 25 degrees C using the statistically weighted free energies of all feasible conformations for the Cys and Cys (-) dipeptides in the gas phase and solvation free energies, which is consistent with the observed values of 8.3 and 8.22 +/- 0.16.

Use of electronic critical care flow sheet data to predict unplanned extubation in ICUs.

This study utilized critical care flow sheet data to develop prediction models for unplanned extubation. A total of 5180 patients with 5412 cases of endotracheal tube extubation treated in a tertiary care teaching hospital were evaluated. A total of 60 extubation cases were classified as unplanned, and 5352 as planned. Features documented in the critical care flow sheet for the 24 h prior to extubation were grouped into those with recording frequencies ≤3 and >3. The nearest values to the extubation were identified for all features. For features recorded >3 times, the maximum, minimum, mean, and recording frequencies were calculated. Univariate analyses were performed to select features for inclusion in multivariate analyses. Three multivariate logistic regression models were compared. Model 1 contained only the nearest value, Model 2 added a recording frequency, and Model 3 replaced the nearest value with the maximum, minimum, or mean that had the highest effect size for each feature recorded >3 times. Univariate analyses showed that 18 features differed significantly between the unplanned extubation and control groups. These included vital signs (e.g., pulse and respiration rates, body temperature), ventilator parameters (e.g., minute volume, peak pressure), and consciousness indicators (e.g., Glasgow coma scale score, Richmond agitation sedation scale score, motor power). On all three multivariate analyses, the Glasgow coma scale score, pulse rate, and peak pressure were statistically significant. The frequency of patient positioning (Model 2) and the minimum respiration rate (Model 3) were also significant. Area under the curve, sensitivity, and positive and negative predictive values improved slightly from Model 1 to Model 2 and from Model 2 to Model 3. This study found that minute volume, peak pressure, and motor power are significant risk factors for unplanned extubation that have not been previously reported. Recording frequency, which reflects how often nursing activities were provided, was also a useful predictor. The indicators identified in this study may help to predict and prevent unplanned extubation in clinical settings.