In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5′ splice sites

We have found that two previously reported exonic mutations in the PINK1 and PARK7 genes affect pre-mRNA splicing. To develop an algorithm to predict underestimated splicing consequences of exonic mutations at the 5′ splice site, we constructed and analyzed 31 minigenes carrying exonic splicing mutations and their derivatives. We also examined 189 249 U2-dependent 5′ splice sites of the entire human genome and found that a new variable, the SD-Score, which represents a common logarithm of the frequency of a specific 5′ splice site, efficiently predicts the splicing consequences of these minigenes. We also employed the information contents (Ri) to improve the prediction accuracy. We validated our algorithm by analyzing 32 additional minigenes as well as 179 previously reported splicing mutations. The SD-Score algorithm predicted aberrant splicings in 198 of 204 sites (sensitivity = 97.1%) and normal splicings in 36 of 38 sites (specificity = 94.7%). Simulation of all possible exonic mutations at positions −3, −2 and −1 of the 189 249 sites predicts that 37.8, 88.8 and 96.8% of these mutations would affect pre-mRNA splicing, respectively. We propose that the SD-Score algorithm is a practical tool to predict splicing consequences of mutations affecting the 5′ splice site

Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities

We developed a simple algorithm, i-Score (inhibitory-Score), to predict active siRNAs by applying a linear regression model to 2431 siRNAs. Our algorithm is exclusively comprised of nucleotide (nt) preferences at each position, and no other parameters are taken into account. Using a validation dataset comprised of 419 siRNAs, we found that the prediction accuracy of i-Score is as good as those of s-Biopredsi, ThermoComposition21 and DSIR, which employ a neural network model or more parameters in a linear regression model. Reynolds and Katoh also predict active siRNAs efficiently, but the numbers of siRNAs predicted to be active are less than one-eighth of that of i-Score. We additionally found that exclusion of thermostable siRNAs, whose whole stacking energy (ΔG) is less than −34.6 kcal/mol, improves the prediction accuracy in i-Score, s-Biopredsi, ThermoComposition21 and DSIR. We also developed a universal target vector, pSELL, with which we can assay an siRNA activity of any sequence in either the sense or antisense direction. We assayed 86 siRNAs in HEK293 cells using pSELL, and validated applicability of i-Score and the whole ΔG value in designing siRNAs

Renewable Chemicals: Dehydroxylation of Glycerol and Polyols

The production of renewable chemicals is gaining attention over the past few years. The natural resources from which they can be derived in a sustainable way are most abundant in sugars, cellulose and hemicellulose. These highly functionalized molecules need to be de-functionalized in order to be feedstocks for the chemical industry. A fundamentally different approach to chemistry thus becomes necessary, since the traditionally employed oil-based chemicals normally lack functionality. This new chemical toolbox needs to be designed to guarantee the demands of future generations at a reasonable price. The surplus of functionality in sugars and glycerol consists of alcohol groups. To yield suitable renewable chemicals these natural products need to be defunctionalized by means of dehydroxylation. Here we review the possible approaches and evaluate them from a fundamental chemical aspect

Attitudes and Opinions of Elderly Patients and Family Caregivers on End-of-Life Care Discussion

Background : End-of-life (EOL) care decisions have become an urgent issue in Korea in response to recent legislation called the Life-Sustaining Treatment Decision Act of 2016. The present study attempted to explore attitudes and opinions on EOL discussion among elderly patients and their family caregivers since communication regarding EOL care has been argued to be a major premise leading to the best decision making. Methods : The attitudes and opinions of elderly patients and their family caregivers were solicited through focus group interviews. The final sample consisted of 12 patients and 16 family members. Results : Guided by content analysis, 5 themes were revealed. The identified themes were individual approach for delivering bad news and stakeholders involved in the discussion, contradictory attitudes toward advance care planning, mutual understanding, hope for the EOL care discussion process, and resistance to discussion of hospice-palliative care. Conclusion : Study findings suggested that an approach focusing on the individualized needs of patients and family members is required in EOL care discussion for elderly patients

Advance Directives and Factors Associated with the Completion in Patients with Heart Failure

Advance directive (AD) has been underutilized among patients with heart failure (HF). This study was performed to explore the ADs and examine factors associated with the completion of an AD survey in patients with HF. In a descriptive, correlational study, data on end-of-life values, treatment directives, and proxy (Korean-Advance Directive (K-AD) questionnaire) and factors associated with K-AD completion were collected among HF patients during outpatient visits. Of 67 patients (age, 67 years; male, 61.2%), 52.2% completed all or part of the K-AD. Among values, comfortable death was the most preferred (n = 15) followed by avoiding family burden (n = 6). In those completers, preferences for hospice care, cardiopulmonary resuscitation, ventilation support, and hemodialysis were 68.6%, 42.9%, 28.6%, and 28.6%, respectively. Female sex (odds ratio (OR) = 0.167), poorer HF prognosis (OR = 0.156), and better functional status (OR = 0.905) were associated with less likelihood of completing the AD survey. The findings suggest that in-depth AD discussion needs to be started earlier in patients with HF to facilitate completion of AD, especially in female patients. Future research should investigate if early discussion of ADs as part of advance care planning with integration into standard care of HF facilitates the documentation of ADs

Trends in the effect of COVID-19 on consultations for persons with clinical and subclinical eating disorders

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has increased the risk of individuals developing eating disorders and has exacerbated existing eating disorders. This observational study investigated the impact of the COVID-19 pandemic on patients with clinical and subclinical eating disorders. Methods This study was conducted over a period of four years: two years before and after the onset of the COVID-19 pandemic in Japan. We recorded the number and types of consultations provided by the Eating Disorder Treatment and Support Center coordinator. For subgroup analysis, data were classified by age, body mass index, and source of consultation, including patients, families, and personnel. The Seasonal Decomposition of Time Series by Loess was used for time series analysis. Results The total number of consultations increased after the start of the pandemic and peaked around the beginning of 2022, before subsequently falling despite the increase in the number of COVID-19 infections. A similar trend was observed in patients aged 10–29 years. The study period coincided with social isolation and school/college/university closures. Conclusions The number of eating disorder consultations increased after the start of the pandemic. Although COVID-19 infections persisted, the pandemic’s impact was transient

Validation of the Decisional Conflict Scale for Evaluating Advance Care Decision Conflict in Community-dwelling Older Adults

Purpose: Decisional conflict is a significant and important barrier in end-of-life care planning, and it is often encountered in health professionals' discussions with patients and their families. Little is known about the measurement of decisional conflict, and existing measures are not suitable for all contexts. In this study, psychometric properties of the Decisional Conflict Scale, which was translated for the first time into Korean [Korean version of DCS (K-DCS)], were examined. Methods: A sample of 273 community-dwelling elders was surveyed (mean age: 77.26 years; 80.2% women). Internal consistency reliability and stability reliability were tested by calculating Cronbach α and Pearson's correlation coefficients. Exploratory factor analysis and logistic regression analyses were performed to test validity. Results: Reliability of the K-DCS was acceptable with Cronbach α =.87; test-retest correlation r = .76. Factor analysis showed a two-factor structure with nine items: informed/values clarity and uncertainty. Concordance between K-DCS and the four treatment directives was significant (kappa values ≥.78). Controlling for age and gender, those with decision implementation were more likely to implement their decisions on tube feeding (odds ratio = 5.15, p = .033) and hospice care (odds ratio = 2.83, p = .017). Conclusion: The K-DCS appears to be a valid measure to evaluate decisional conflict about advance directives in community-dwelling Korean older adults. Further validation of the K-DCS is warranted, though caution should be exercised in using subscales because of differences in decisional contexts. Keywords: advance directives, community, elderly, psychometric