The Benefits of a Person-centered Social Program for Community-dwelling People with Dementia and Caregivers: An Interpretative Phenomenological Analysis

This qualitative study aimed to explore the experience and impact of a person-centered, social program on community-dwelling people with dementia and their caregivers. I conducted semi-structured interviews with five dyads, each with a person with dementia and that person’s caregiver, 7-8 months after the program ended to assess persistence of the program’s impact. Interviews were analyzed using interpretative phenomenological analysis involving in-depth analysis of a small number of cases. Three themes emerged among people with dementia: 1) Participation in activities supporting self-identity; 2) The value of newly established intergenerational relationships; and 3) Empowerment and the student partner’s attitude. These findings suggest taking part in a person-centered, social program promoted participation in activities supporting the self-identity of people with dementia and establishment of satisfying relationships with student partners. The student partner’s attitude influenced the level of empowerment for the person with dementia in relation to participation in meaningful activities and relationships. Three themes also emerged among caregivers: 1) Benefits of the program for caregivers; 2) Initial expectations and the later perspectives of caregivers about the program; and 3) Conflicting values and perspectives between caregivers and spouses. Benefits identified by caregivers included feeling enjoyment and satisfaction of their spouses with dementia from participation in the program; having a fun time with a friend or alone separate from the spouse; and a chance to socialize with a younger person while assuming a role as an older friend or parent. Participation in the program provided a sustained benefit to one couple in particular even 7 months after the program ended, by encouraging the caregiver to resume arranging activities the couple once enjoyed but now had difficulty pursuing. Conflicting perspectives noted between people with dementia and the caregivers illustrate needs and desires expressed by both people with dementia and their caregivers need to be considered when structuring social partner activities. These findings address a gap in the literature by documenting how a person-centered, social program benefits both community-dwelling people with dementia and their family caregivers, with implications for providing insightful opportunities for social engagement as part of occupational therapy and other health care practices

De novo prediction of PTBP1 binding and splicing targets reveals unexpected features of its RNA recognition and function.

The splicing regulator Polypyrimidine Tract Binding Protein (PTBP1) has four RNA binding domains that each binds a short pyrimidine element, allowing recognition of diverse pyrimidine-rich sequences. This variation makes it difficult to evaluate PTBP1 binding to particular sites based on sequence alone and thus to identify target RNAs. Conversely, transcriptome-wide binding assays such as CLIP identify many in vivo targets, but do not provide a quantitative assessment of binding and are informative only for the cells where the analysis is performed. A general method of predicting PTBP1 binding and possible targets in any cell type is needed. We developed computational models that predict the binding and splicing targets of PTBP1. A Hidden Markov Model (HMM), trained on CLIP-seq data, was used to score probable PTBP1 binding sites. Scores from this model are highly correlated (ρ = -0.9) with experimentally determined dissociation constants. Notably, we find that the protein is not strictly pyrimidine specific, as interspersed Guanosine residues are well tolerated within PTBP1 binding sites. This model identifies many previously unrecognized PTBP1 binding sites, and can score PTBP1 binding across the transcriptome in the absence of CLIP data. Using this model to examine the placement of PTBP1 binding sites in controlling splicing, we trained a multinomial logistic model on sets of PTBP1 regulated and unregulated exons. Applying this model to rank exons across the mouse transcriptome identifies known PTBP1 targets and many new exons that were confirmed as PTBP1-repressed by RT-PCR and RNA-seq after PTBP1 depletion. We find that PTBP1 dependent exons are diverse in structure and do not all fit previous descriptions of the placement of PTBP1 binding sites. Our study uncovers new features of RNA recognition and splicing regulation by PTBP1. This approach can be applied to other multi-RRM domain proteins to assess binding site degeneracy and multifactorial splicing regulation

Aiding Reflective Navigation in a Dynamic Information Landscape: A Challenge for Educational Psychology

Open access to information is now a universal phenomenon thanks to rapid technological developments across the globe. This open and universal access to information is a key value of democratic societies because, in principle, it supports well-informed decision-making on individual, local, and global matters. In practice, however, without appropriate readiness for navigation in a dynamic information landscape, such access to information can become a threat to public health, safety, and economy, as the COVID-19 pandemic has shown. In the past, this readiness was often conceptualized in terms of adequate literacy levels, but the contemporarily observed highest-ever literacy levels have not immunized our societies against the risks of misinformation. Therefore, in this Perspective, we argue that democratisation of access to information endows citizens with new responsibilities, and second, these responsibilities demand readiness that cannot be reduced to mere literacy levels. In fact, this readiness builds on individual adequate literacy skills, but also requires rational thinking and awareness of own information processing. We gather evidence from developmental, educational, and cognitive psychology to show how these aspects of readiness could be improved through education interventions, and how they may be related to healthy work-home balance and self-efficacy. All these components of education are critical to responsible global citizenship and will determine the future direction of our societies

De Novo Prediction of PTBP1 Binding and Splicing Targets Reveals Unexpected Features of Its RNA Recognition and Function

The splicing regulator Polypyrimidine Tract Binding Protein (PTBP1) has four RNA binding domains that each binds a short pyrimidine element, allowing recognition of diverse pyrimidine-rich sequences. This variation makes it difficult to evaluate PTBP1 binding to particular sites based on sequence alone and thus to identify target RNAs. Conversely, transcriptome-wide binding assays such as CLIP identify many in vivo targets, but do not provide a quantitative assessment of binding and are informative only for the cells where the analysis is performed. A general method of predicting PTBP1 binding and possible targets in any cell type is needed. We developed computational models that predict the binding and splicing targets of PTBP1. A Hidden Markov Model (HMM), trained on CLIP-seq data, was used to score probable PTBP1 binding sites. Scores from this model are highly correlated (ρ = −0.9) with experimentally determined dissociation constants. Notably, we find that the protein is not strictly pyrimidine specific, as interspersed Guanosine residues are well tolerated within PTBP1 binding sites. This model identifies many previously unrecognized PTBP1 binding sites, and can score PTBP1 binding across the transcriptome in the absence of CLIP data. Using this model to examine the placement of PTBP1 binding sites in controlling splicing, we trained a multinomial logistic model on sets of PTBP1 regulated and unregulated exons. Applying this model to rank exons across the mouse transcriptome identifies known PTBP1 targets and many new exons that were confirmed as PTBP1-repressed by RT-PCR and RNA-seq after PTBP1 depletion. We find that PTBP1 dependent exons are diverse in structure and do not all fit previous descriptions of the placement of PTBP1 binding sites. Our study uncovers new features of RNA recognition and splicing regulation by PTBP1. This approach can be applied to other multi-RRM domain proteins to assess binding site degeneracy and multifactorial splicing regulation

Comparison of sedation outcome according to the dose of chloral hydrate in children requiring laceration repair

Purpose To compare the sedation outcome according to the dose of per os chloral hydrate in children who underwent laceration repair in the emergency department (ED). Methods This retrospective study was performed to the children who underwent sedation using chloral hydrate for laceration repair in the ED from January 2015 through November 2015. A total of 370 children aged younger than 6 years underwent the sedation. We compared the induction time, duration of sedation, and ED length of stay (EDLOS) between the single dose (50 mg/kg) and additional dose (plus 25 mg/kg) groups. Results Of 370 children, 335 (90.5%) were sedated successfully, 284 (76.8%) were sedated with initial dose (the single dose group), and 51 (13.8%) were sedated with additional dose (the additional dose group). The induction time and EDLOS were longer in the additional dose group (induction time: 31.0 ± 17.2 minutes vs. 96.2 ± 25.4 minutes, P < 0.001; EDLOS: 137.2 ± 35.5 minutes vs. 193.0 ± 36.0 minutes, P < 0.001). The duration of sedation showed no difference between the 2 groups (44.4 ± 24.0 minutes vs. 42.0 ± 20.8 minutes; P = 0.500). No one had serious adverse reactions. Conclusion Additional dose of chloral hydrate can increase the induction time and EDLOS without increasing the duration of sedation and causing serious adverse reactions. This information may improve the efficiency of ED workflow when shared with parents of the children

SNP@Domain: a web resource of single nucleotide polymorphisms (SNPs) within protein domain structures and sequences.

The single nucleotide polymorphisms (SNPs) in conserved protein regions have been thought to be strong candidates that alter protein functions. Thus, we have developed SNP@Domain, a web resource, to identify SNPs within human protein domains. We annotated SNPs from dbSNP with protein structure-based as well as sequence-based domains: (i) structure-based using SCOP and (ii) sequence-based using Pfam to avoid conflicts from two domain assignment methodologies. Users can investigate SNPs within protein domains with 2D and 3D maps. We expect this visual annotation of SNPs within protein domains will help scientists select and interpret SNPs associated with diseases. A web interface for the SNP@Domain is freely available at http://snpnavigator.net/ and from http://bioportal.net/.This project was supported by the Korean Ministry of Science and Technology (MOST) under grant number M10508040002-05N0804-00210 and M10407010001-05N0701-00100. Y.B.C. is supported by Biogreen21 program (20050401-034-791-006-03-00 and 20050301-034-481-006-02-00). Funding to pay the Open Access publication charges for this article was provided by M10407010001-05N0701-00100 grant of MOST

A time-dependent subdistribution hazard model for major dental treatment events in cancer patients: a nationwide cohort study

Abstract Background Dental care in cancer patients tends to be less prioritized. However, limited research has focused on major dental treatment events in cancer patients after the diagnosis. This study aimed to examine dental treatment delays in cancer patients compared to the general population using a national claims database in South Korea. Method The Korea National Health Insurance Service-National Sample Cohort version 2.0, collected from 2002 to 2015, was analyzed. Treatment events were considered for stomatitis, tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease. For each considered event, time-dependent hazard ratios and associated 95% confidence intervals were calculated by applying a subdistribution hazard model with time-varying covariates. Mortality was treated as a competing event. Subgroup analyses were conducted by type of cancer. Results The time-dependent subdistribution hazard ratios (SHRs) of stomatitis treatment were greater than 1 in cancer patients in all time intervals, 2.04 within 30 days after cancer diagnosis, and gradually decreased to 1.15 after 5 years. The SHR for tooth loss was less than 0.70 within 3 months after cancer diagnosis and increased to 1 after 5 years. The trends in SHRs of treatment events for other dental diseases were similar to those observed for tooth loss. Subgroup analyses by cancer type suggested that probability of all dental treatment event occurrence was higher in head and neck cancer patients, particularly in the early phase after cancer diagnosis. Conclusion Apart from treatments that are associated with cancer therapy, dental treatments in cancer patients are generally delayed and cancer patients tend to refrain from dental treatments. Consideration should be given to seeking more active and effective means for oral health promotion in cancer patients

Developmental regulation of myeloerythroid progenitor function by the Lin28b–let-7–Hmga2 axis

For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood. In this study, we find that expression of the heterochronic factor Lin28b decreases in common myeloid progenitors during hematopoietic maturation to adulthood in mice. This decrease in Lin28b coincides with accumulation of mature let-7 microRNAs, whose biogenesis is regulated by Lin28 proteins. We find that inhibition of let-7 in the adult hematopoietic system recapitulates fetal erythroid-dominant hematopoiesis. Conversely, deletion of Lin28b or ectopic activation of let-7 microRNAs in the fetal state induces a shift toward adult-like myeloid-dominant output. Furthermore, we identify Hmga2 as an effector of this genetic switch. These studies provide the first detailed analysis of the roles of endogenous Lin28b and let-7 in the timing of hematopoietic states during development

LIN28 phosphorylation by MAPK/ERK couples signaling to the post-transcriptional control of pluripotency

Signaling and post-transcriptional gene control are both critical for the regulation of pluripotency1,2, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein (RBP), has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA (miRNA) biogenesis and direct modulation of mRNA translation3. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells (PSCs), which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced LIN28’s effect on its direct mRNA targets, revealing a mechanism that uncouples LIN28’s let-7-dependent and independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naïve to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signaling, post-transcriptional gene control, and cell fate regulation

Health benefits of serious involvement in leisure activities among older Korean adults

The existing literature suggests that serious engagement in leisure activities leads to happiness, life satisfaction, and successful aging among older adults. This qualitative study was used to examine the benefits of serious involvement in leisure activities among older Korean adults who were members of a sports club. Using an analytic data analysis, we identified three main themes associated with the benefits of serious engagement in leisure activities: 1) the experience of psychological benefits, 2) the creation of social support, and 3) the enhancement of physical health. These themes indicate that, through serious involvement in certain physical activities, participants gain various health benefits, which may contribute to successful aging