Financial Hardship: A Qualitative Study Exploring Perspectives of Seriously Ill Patients and Their Family.

CONTEXT: Seriously ill patients, such as those who experience critical illness, and their families experience a variety of poor outcomes, including financial hardship. However, little is known about the ways in which these seriously ill patients and their families experience financial hardship. OBJECTIVE: To examine seriously ill patients' and families' experiences of financial hardship and perspectives on addressing these concerns during and after critical illness. METHODS: We conducted a thematic analysis of semi-structured interviews with seriously ill patients who recently experienced a critical care hospitalization (n=15) and family caregivers of these patients (n=18). RESULTS: Our analysis revealed three themes: 1) Prioritizing Survival and Recovery; 2) Living with Uncertainty-including experiences of prolonged uncertainty, navigating bureaucratic barriers, and long-term worries; and 3) Preferences for Financial Guidance. Our results suggest patients and families prioritize survival over financial hardship initially, and feelings of uncertainty about finances persist. However, patients and family caregivers are reluctant to have their physicians address financial hardship. CONCLUSIONS: Our findings suggest that the acute and time sensitive nature of treatment decisions in critical care settings provides a unique context for experiences of financial hardship. Additional research is needed to better understand these experiences and design context-sensitive interventions to mitigate financial hardship and associated poor patient- and family-centered outcomes.

Applying human-centered design to adapt the Jumpstart Guide for goals-of-care discussions in persons living with dementia.

BACKGROUND: Goals-of-care discussions (GOCD) are uncommon in persons living with dementia (PLWD) despite the likelihood of eventual loss of decisional capacity in the population. The Jumpstart Guide, an existing serious illness communication priming tool, can improve GOCD in certain populations, but has not previously been adapted for use among PLWD and their caregivers. METHODS: Using human-centered design (HCD), we adapted the Jumpstart Guide for use with PLWD and their caregivers. We conducted qualitative interviews with clinicians and caregivers of PLWD. Six team members conducted qualitative rapid analysis of interviews leading to the development of summary templates and integrative matrices. Four iterations of the Jumpstart Guide led to the final version. RESULTS: Thirteen clinicians and 11 caregivers were interviewed. Interviews provided key insights into the unique barriers PLWD and their caregivers face during GOCD, including discomfort with accepting a dementia diagnosis and concern with using "serious illness" to describe dementia, as is commonly done in palliative care. Clinicians described differences in GOCD with PLWD compared to other serious illnesses, and the challenge of getting patients and families to think about future health states. Interviews led to Jumpstart Guide adaptations in the following domains: (1) format and structure, (2) content, and (3) specific language. Suggested changes included prioritizing naming a decision-maker, changing conversation prompts to improve accessibility and understandability, ensuring the Jumpstart Guide could be used with patients as well as their caregivers, and altering language to avoid references to "serious illness" and "abilities." CONCLUSION: Using HCD yielded valuable insights from clinicians and caregivers about the unique barriers to conducting GOCD among PLWD and their caregivers. These insights were used to adapt the Jumpstart Guide for use with PLWD and their caregivers, which is currently being tested in a pragmatic randomized controlled trial in outpatient clinics.

Disability and Place of Death in Older Americans: The Moderating Role of Household Wealth.

CONTEXT: Home-based deaths are increasing, yet, how wealth influences where people die in the presence of disability remains unknown. OBJECTIVE: To examine place of death by help with (instrumental) activities of daily living (I/ADLs) at the end of life (EOL) and the modifying role of wealth. METHODS: Retrospective study of decedents from the Health and Retirement Study (n = 13,210). The exposure was intensity of help with I/ADLs at the EOL (no help/ lower intensity/higher intensity). The outcome was place of death (hospital/nursing home/home). Household wealth was an effect modifier with six categories: ≤$0, first-fifth quintile. Covariates included age, gender, race, marital status at the EOL, last place of residence, and receipt of hospice care. We used multinomial logit regression models with estimates reported as average marginal effects (AMEs). RESULTS: Mean age was 79.8 years; 53.2% were female. In the adjusted models, compared to not receiving help at EOL, receiving higher-intensity help was associated with a lower probability of dying in a hospital (AME = -3.8 percentage points (pp), 95% CI = -6.3 to -1.3) and a higher probability of dying at home (AME = 3.6 pp, 95% CI = 1.4-5.7). Associations were most pronounced among decedents in the top two wealth quintiles; older adults who received higher-intensity help had a lower probability of dying in a hospital (AME = -9.0 pp, 95% CI = -14.8 to -3.1), and a higher probability of dying at home (AME = 8.4 pp, 95% CI = 3.8-13.0). CONCLUSION: Receiving higher intensity of help with I/ADLs was associated with lower likelihood of dying in a hospital, and higher likelihood of dying at home, particularly among older adults with greater wealth.

Intervention to Promote Communication About Goals of Care for Hospitalized Patients With Serious Illness: A Randomized Clinical Trial.

Importance: Discussions about goals of care are important for high-quality palliative care yet are often lacking for hospitalized older patients with serious illness. Objective: To evaluate a communication-priming intervention to promote goals-of-care discussions between clinicians and hospitalized older patients with serious illness. Design, Setting, and Participants: A pragmatic, randomized clinical trial of a clinician-facing communication-priming intervention vs usual care was conducted at 3 US hospitals within 1 health care system, including a university, county, and community hospital. Eligible hospitalized patients were aged 55 years or older with any of the chronic illnesses used by the Dartmouth Atlas project to study end-of-life care or were aged 80 years or older. Patients with documented goals-of-care discussions or a palliative care consultation between hospital admission and eligibility screening were excluded. Randomization occurred between April 2020 and March 2021 and was stratified by study site and history of dementia. Intervention: Physicians and advance practice clinicians who were treating the patients randomized to the intervention received a 1-page, patient-specific intervention (Jumpstart Guide) to prompt and guide goals-of-care discussions. Main Outcomes and Measures: The primary outcome was the proportion of patients with electronic health record-documented goals-of-care discussions within 30 days. There was also an evaluation of whether the effect of the intervention varied by age, sex, history of dementia, minoritized race or ethnicity, or study site. Results: Of 3918 patients screened, 2512 were enrolled (mean age, 71.7 [SD, 10.8] years and 42% were women) and randomized (1255 to the intervention group and 1257 to the usual care group). The patients were American Indian or Alaska Native (1.8%), Asian (12%), Black (13%), Hispanic (6%), Native Hawaiian or Pacific Islander (0.5%), non-Hispanic (93%), and White (70%). The proportion of patients with electronic health record-documented goals-of-care discussions within 30 days was 34.5% (433 of 1255 patients) in the intervention group vs 30.4% (382 of 1257 patients) in the usual care group (hospital- and dementia-adjusted difference, 4.1% [95% CI, 0.4% to 7.8%]). The analyses of the treatment effect modifiers suggested that the intervention had a larger effect size among patients with minoritized race or ethnicity. Among 803 patients with minoritized race or ethnicity, the hospital- and dementia-adjusted proportion with goals-of-care discussions was 10.2% (95% CI, 4.0% to 16.5%) higher in the intervention group than in the usual care group. Among 1641 non-Hispanic White patients, the adjusted proportion with goals-of-care discussions was 1.6% (95% CI, -3.0% to 6.2%) higher in the intervention group than in the usual care group. There was no evidence of differential treatment effects of the intervention on the primary outcome by age, sex, history of dementia, or study site. Conclusions and Relevance: Among hospitalized older adults with serious illness, a pragmatic clinician-facing communication-priming intervention significantly improved documentation of goals-of-care discussions in the electronic health record, with a greater effect size in racially or ethnically minoritized patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04281784.

Structure-Based Regulatory Role for the 5'UTR of RCNMV RNA2.

Red clover necrotic mosaic virus (RCNMV) is a segmented positive-strand RNA virus consisting of RNA1 and RNA2. Previous studies demonstrated that efficient translation of RCNMV RNA2 requires de novo synthesis of RNA2 during infections, suggesting that RNA2 replication is required for its translation. We explored a potential mechanism underlying the regulation of replication-associated translation of RNA2 by examining RNA elements in its 5' untranslated region (5'UTR). Structural analysis of the 5'UTR suggested that it can form two mutually exclusive configurations: a more thermodynamically stable conformation, termed the 5'-basal stem structure (5'BS), in which 5'-terminal sequences are base paired, and an alternative conformation, where the 5'-end segment is single stranded. Functional mutational analysis of the 5'UTR structure indicated that (i) 43S ribosomal subunits enter at the very 5'-end of RNA2; (ii) the alternative conformation, containing unpaired 5'-terminal nucleotides, mediates efficient translation; (iii) the 5'BS conformation, with a paired 5'-end segment, supresses translation; and (iv) the 5'BS conformation confers stability to RNA2 from 5'-to-3' exoribonuclease Xrn1. Based on our results, we suggest that during infections, newly synthesized RNA2s transiently adopt the alternative conformation to allow for efficient translation, then refold into the 5'BS conformation, which supresses translation and promotes efficient RNA2 replication. The potential advantages of this proposed 5'UTR-based regulatory mechanism for coordinating RNA2 translation and replication are discussed.

On the same page? A qualitative study of shared mental models in an interprofessional, inter-organizational team implementing goal-oriented care.

Goal-oriented care is an approach to care delivery that uses patient-identified goals to drive care planning. Implementing goal-oriented care requires team members to cognitively shift the focus from "what is the matter" to "what matters to patients," and align their mental models of what it means to care for patients. Yet, no empirical studies of goal-oriented care apply evidence from the cognitive sciences, such as Shared Mental Model (SMM) theory. We conducted a qualitative case study of an interprofessional team that adopted goal-oriented care in Vermont, US (n = 18). Guided by SMM theory, we distinguished between task-related and team-related mental models. We used framework analysis and qualitative content analysis to determine mental model content and similarity. The most shared content areas were operationalizing goal-oriented care, engaging in formal and informal communication, taking a "whole-person" approach, taking a team approach, and building trusting relationships with patients and with other team members. Trust was the only construct that spanned both task and team mental model categories, highlighting the importance of both intra-team trust and provider-patient trust to the implementation of goal-oriented care. Team members developed SMMs through training, regular meetings, and interactions during care delivery. This study provides insight into the cognitive mechanisms that underlie team-based goal-oriented care delivery, which can be used to inform implementation, training content, and future research.

Improving communication about goals of care for hospitalized patients with serious illness: Study protocol for two complementary randomized trials.

BACKGROUND: Although goals-of-care discussions are important for high-quality palliative care, this communication is often lacking for hospitalized older patients with serious illness. Electronic health records (EHR) provide an opportunity to identify patients who might benefit from these discussions and promote their occurrence, yet prior interventions using the EHR for this purpose are limited. We designed two complementary yet independent randomized trials to examine effectiveness of a communication-priming intervention (Jumpstart) for hospitalized older adults with serious illness. METHODS: We report the protocol for these 2 randomized trials. Trial 1 has two arms, usual care and a clinician-facing Jumpstart, and is a pragmatic trial assessing outcomes with the EHR only (n = 2000). Trial 2 has three arms: usual care, clinician-facing Jumpstart, and clinician- and patient-facing (bi-directional) Jumpstart (n = 600). We hypothesize the clinician-facing Jumpstart will improve outcomes over usual care and the bi-directional Jumpstart will improve outcomes over the clinician-facing Jumpstart and usual care. We use a hybrid effectiveness-implementation design to examine implementation barriers and facilitators. OUTCOMES: For both trials, the primary outcome is EHR documentation of a goals-of-care discussion within 30 days of randomization; additional outcomes include intensity of end-of-life care. Trial 2 also examines patient- or family-reported outcomes assessed by surveys targeting 3-5 days and 4-8 weeks after randomization including quality of goals-of-care communication, receipt of goal-concordant care, and psychological symptoms. CONCLUSIONS: This novel study incorporates two complementary randomized trials and a hybrid effectiveness-implementation approach to improve the quality and value of care for hospitalized older adults with serious illness. CLINICAL TRIALS REGISTRATION: STUDY00007031-A and STUDY00007031-B.

Trans-Activator Binding Site Context in RCNMV Modulates Subgenomic mRNA Transcription.

Many positive-sense RNA viruses transcribe subgenomic (sg) mRNAs during infections that template the translation of a subset of viral proteins. Red clover necrotic mosaic virus (RCNMV) expresses its capsid protein through the transcription of a sg mRNA from RNA1 genome segment. This transcription event is activated by an RNA structure formed by base pairing between a trans-activator (TA) in RNA2 and a trans-activator binding site (TABS) in RNA1. In this study, the impact of the structural context of the TABS in RNA1 on the TA-TABS interaction and sg mRNA transcription was investigated using in vitro and in vivo approaches. The results (i) generated RNA secondary structure models for the TA and TABS, (ii) revealed that the TABS is partially base paired with proximal upstream sequences, which limits TA access, (iii) demonstrated that the aforementioned intra-RNA1 base pairing involving the TABS modulates the TA-TABS interaction in vitro and sg mRNA levels during infections, and (iv) revealed that the TABS in RNA1 can be modified to mediate sg mRNA transcription in a TA-independent manner. These findings advance our understanding of transcriptional regulation in RCNMV and provide novel insights into the origin of the TA-TABS interaction.

RNA Structure Protects the 5' End of an Uncapped Tombusvirus RNA Genome from Xrn Digestion.

One of the many challenges faced by RNA viruses is the maintenance of their genomes during infections of host cells. Members of the family Tombusviridae are plus-strand RNA viruses with unmodified triphosphorylated genomic 5' termini. The tombusvirus Carnation Italian ringspot virus was used to investigate how it protects its RNA genome from attack by 5'-end-targeting degradation enzymes. In vivo and in vitro assays were employed to determine the role of genomic RNA structure in conferring protection from the 5'-to-3' exoribonuclease Xrn. The results revealed that (i) the CIRV RNA genome is more resistant to Xrn than its sg mRNAs, (ii) the genomic 5'-untranslated region (UTR) folds into a compact RNA structure that effectively and independently prevents Xrn access, (iii) the RNA structure limiting 5' access is formed by secondary and tertiary interactions that function cooperatively, (iv) the structure is also able to block access of RNA pyrophosphohydrolase to the genomic 5' terminus, and (v) the RNA structure does not stall an actively digesting Xrn. Based on its proficiency at impeding Xrn 5' access, we have termed this 5'-terminal structure an Xrn-evading RNA, or xeRNA. These and other findings demonstrate that the 5'UTR of the CIRV RNA genome folds into a complex structural conformation that helps to protect its unmodified 5' terminus from enzymatic decay during infections. IMPORTANCE The plus-strand RNA genomes of plant viruses in the large family Tombusviridae are not 5' capped. Here, we explored how a species in the type genus Tombusvirus protects its genomic 5' end from cellular nuclease attack. Our results revealed that the 5'-terminal sequence of the CIRV genome folds into a complex RNA structure that limits access of the 5'-to-3' exoribonuclease Xrn, thereby protecting it from processive degradation. The RNA conformation also impeded access of RNA pyrophosphohydrolase, which converts 5'-triphosphorylated RNA termini into 5'-monophosphorylated forms, the preferred substrate for Xrn. This study represents the first report of a higher-order RNA structure in an RNA plant virus genome independently conferring resistance to 5'-end-attacking cellular enzymes.

Facilitating communication for critically ill patients and their family members: Study protocol for two randomized trials implemented in the U.S. and France.

BACKGROUND: Critically-ill patients and their families suffer a high burden of psychological symptoms due, in part, to many transitions among clinicians and settings during and after critical illness, resulting in fragmented care. Communication facilitators may help. DESIGN AND INTERVENTION: We are conducting two cluster-randomized trials, one in the U.S. and one in France, with the goal of evaluating a nurse facilitator trained to support, model, and teach communication strategies enabling patients and families to secure care consistent with patients' goals, beginning in ICU and continuing for 3 months. PARTICIPANTS: We will randomize 376 critically-ill patients in the US and 400 in France to intervention or usual care. Eligible patients have a risk of hospital mortality of greater than15% or a chronic illness with a median survival of approximately 2 years or less. OUTCOMES: We assess effectiveness with patient- and family-centered outcomes, including symptoms of depression, anxiety, and post-traumatic stress, as well as assessments of goal-concordant care, at 1-, 3-, and 6-months post-randomization. The primary outcome is family symptoms of depression over 6 months. We also evaluate whether the intervention improves value by reducing utilization while improving outcomes. Finally, we use mixed methods to explore implementation factors associated with implementation outcomes (acceptability, fidelity, acceptability, penetration) to inform dissemination. Conducting the trial in U.S. and France will provide insights into differences and similarities between countries. CONCLUSIONS: We describe the design of two randomized trials of a communication facilitator for improving outcomes for critically ill patients and their families in two countries.

Goal-Oriented Care: A Catalyst for Person-Centred System Integration.

INTRODUCTION: Person-centred integrated care is often at odds with how current health care systems are structured, resulting in slower than expected uptake of the model worldwide. Adopting goal-oriented care, an approach which uses patient priorities, or goals, to drive what kinds of care are appropriate and how care is delivered, may offer a way to improve implementation. DESCRIPTION: This case report presents three international cases of community-based primary health care models in Ottawa (Canada), Vermont (USA) and Flanders (Belgium) that adopted goal-oriented care to stimulate clinical, professional, organizational and system integration. The Rainbow Model of Integrated Care is used to demonstrate how goal-oriented care drove integration at all levels. DISCUSSION: The three cases demonstrate how goal-oriented care has the potential to catalyse integrated care. Exploration of these cases suggests that goal-oriented care can serve to activate formative and normative integration mechanisms; supporting processes that enable integrated care, while providing a framework for a shared philosophy of care. LESSONS LEARNED: By establishing a common vision and philosophy to drive shared processes, goal-oriented care can be a powerful tool to enable integrated care delivery. Offering plenty of opportunities for training in goal-oriented care within and across teams is essential to support this shift.

Expression analysis of LTR-derived miR-1269a and target gene, KSR2 in Sebastes schlegelii.

BACKGROUND: Sebastes schlegelii are an important species of fish found in the coastal areas of the Korea with significant commercial importance. Most studies thus far have been primarily focused on environmental factors; behavioural patterns, aquaculture, diseases and limited genetic studies with little to none related to either microRNAs (miRNAs) or transposable elements (TE). OBJECTIVES: In order to understand biological roles of TE-derived miR-1269a, we examined expression pattern for miR-1269a and its target gene, KSR2, in various tissues of Sebastes schlegelii. Also, we performed luciferase reporter assay in HINAE cells. METHODS: UCSC Genome Browser (https://genome.ucsc.edu/) was used to examine which TE is associated with miR-1269a. For the target genes for miR-1269a, the target genes associated with the miRNA were identified using miRDB (http://www.mirdb.org/) and TargetScan 7.1 (http://www.targetscan.org/vert_71/). A two-step miRNA kit, HB miR Multi Assay Kit™ System. I was used for the analysis of TE-derived miRNA expression patterns. The 3'UTR of KSR2 gene was cloned into the psiCHECK-2 vector. Subsequently co-transfected with miR-1269a mimics to HINAE cells for luciferase reporter assay. RESULTS: MiR-1269a was found to be derived from LTR retrotransposon, MLT2B. LTR-derived miR-1269a was highly expressed in the muscle, liver and gonad tissues of Sebastes schlegelii, but KSR2 revealed high expression in the brain. Co-transfection of KSR2 and miR-1269a mimic to HINAE cells showed high activity of miR-1269a in relation to KSR2. CONCLUSION: LTR-derived miR-1269a showed enhancer activity with relation to KSR2 in Sebastes schlegelii. The data may be used as a foundation for further investigation regarding correlation of miRNA and target genes in addition to other functional studies of biological significance in Sebastes schlegelii.

Genetic features of Haliotis discus hannai by infection of vibrio and virus.

BACKGROUND: Haliotis discus hannai more commonly referred to as the Pacific Abalone is of significant commercial and economical value in South Korea, with it being the second largest producer in the world. Despite this significance there is a lack of genetic studies with regards to the species. Most existing studies focused mainly on environmental factors. OBJECTIVE: To provide a comprehensive review describing the genetic feature of Haliotis discus hannai by infection of vibrio and virus. METHODS: This review summarized the immune response in the Haliotis spp. with regards to immunological genes such as Cathepsin B, C-type lectin and Toll-like receptors. Genetic studies with regards to transposable elements and miRNAs are few and far between. A study identified LTR retrotransposon Ty3/gypsy in the species. As to miRNA, a single study identified numerous miRNAs in the Haliotis discus hannai. CONCLUSION: This paper sought to provide an overview of genetic perspective with regards to immune response genes, transposable elements and miRNAs.

"Whatever happens, happens" challenges of end-of-life communication from the perspective of older adults and family caregivers: a Qualitative study.

BACKGROUND: Effective communication is integral to the delivery of goal-concordant care for older adults and their family caregivers, and yet, it is uncommon in people with serious illness. This study explores the challenges of integrating end-of-life communication into heart failure management from the perspectives of older adults and family caregivers. METHODS: In a qualitative study of older adults with heart failure and their family caregivers, fourteen semi-structured interviews were conducted with 19 participants in Ontario, Canada. The interviews were transcribed verbatim and thematic analysis was applied to analyze the data. RESULTS: Four themes were identified in the context of participants' understanding of illness: 1) trivializing illness-related challenges, 2) positivity in late life, 3) discomfort in having end-of-life conversations, and 4) reluctant to engage despite need. These challenges often intertwine with one another. Most participants had not engaged in end-of-life discussions with their clinicians or family members. CONCLUSION: The findings provide insights that can inform approaches to integrate end-of-life communication for older adults with serious illness and caregivers. The identified challenges highlight a need for end-of-life communication to occur earlier in illness to be able to support individuals throughout the period of decline. In addition, end-of-life communication should be introduced iteratively for those who may not be ready to engage. Alternative approaches to communication are needed to elicit the challenges that patients and caregivers experience throughout the progression of illness to improve care for people nearing the end of life.

Characterization of the Long Terminal Repeat of the Endogenous Retrovirus-derived microRNAs in the Olive Flounder.

Endogenous retroviruses (ERVs) have been identified at different copy numbers in various organisms. The long terminal repeat (LTR) element of an ERV has the capacity to exert regulatory influence as both a promoter and enhancer of cellular genes. Here, we describe olive flounder (OF)-ERV9, derived from chromosome 9 of the olive flounder. OF-ERV9-LTR provide binding sites for various transcription factors and showed enhancer activity. The OF-ERV9-LTR demonstrates high sequence similarity with the 3' untranslated region (UTR) of various genes that also contain seed sequences (TGTTTTG) that bind the LTR-derived microRNA(miRNA), OF-miRNA-307. Additionally, OF-miRNA-307 collaborates with transcription factors located in OF-ERV9-LTR to regulate gene expression. Taken together, our data facilitates a greater understanding of the molecular function of OF-ERV families and suggests that OF-miRNA-307 may act as a super-enhancer miRNA regulating gene activity.

'The Future is Probably Now': Understanding of illness, uncertainty and end-of-life discussions in older adults with heart failure and family caregivers.

BACKGROUND: Earlier end-of-life communication is critical for people with heart failure given the uncertainty and high-risk of mortality in illness. Despite this, end-of-life communication is uncommon in heart failure. Left unaddressed, lack of end-of-life discussions can lead to discordant care at the end of life. OBJECTIVE: This study explores patients' and caregivers' understanding of illness, experiences of uncertainty, and perceptions of end-of-life discussions in advanced illness. DESIGN: Interpretive descriptive qualitative study of older adults with heart failure and family caregivers. Fourteen semi-structured interviews were conducted with 19 participants in Ontario, Canada. Interviews were transcribed verbatim and content analysis was used to analyse the data. MAIN RESULTS: Understanding of illness was shaped by participants' illness-related experiences (e.g. symptoms, hospitalizations and self-care routines) and the ability to adapt to challenges of illness. Participants were knowledgeable of heart failure management, and yet, were limited in their understanding of the consequences of illness. Participants adapted to the challenges of illness which appeared to influence their perception of overall health. Uncertainty reflected participants' inability to connect manifestations of heart failure as part of the progression of illness towards the end of life. Most participants had not engaged in prior end-of-life discussions. CONCLUSION: Detailed knowledge of heart failure management does not necessarily translate to an understanding of the consequences of illness. The ability to adapt to illness-related challenges may delay older adults and family caregivers from engaging in end-of-life discussions. Future research is needed to examine the impact of addressing the consequences of illness in facilitating earlier end-of-life communication.

Expression analysis of miR-221-3p and its target genes in horses.

BACKGROUND: A microRNA (miRNA) is a small non-coding RNA (ncRNA) approximately 20 nucleotides long and it affects gene expression through mRNA cleavage or translational repression. Horses (Equus caballus) have been domesticated and bred to enhance their speed for racing. It has been studied extensively with genetic diversity, origins and evolution. OBJECTIVES: We examined expression patterns of miR-221-3p and its target gene CDKN1C in various horse tissues. METHODS: We used bioinformatic tools to examine target gene, seed region and evolutionary conservation of miR-221-3p. The expression patterns of miR-221-3p and its target gene CDKN1C were analyzed by quantitative polymerase chain reaction (qPCR). RESULTS: Among eight tissues of horse, miR-221-3p was highly expressed in cerebellum and spleen. On the other hand, only medulla was highly expressed in CDKN1C gene. CONCLUSION: Our study provides expression data of miR-221-3p and CDKN1C gene in horse and suggests the fundamental information for future studies in relation to functional importance.

Fully-covered metal stents with endoscopic suturing vs. partially-covered metal stents for benign upper gastrointestinal diseases: a comparative study.

BACKGROUND AND STUDY AIMS: Self-expandable metallic stents (SEMS) have been increasingly used in benign conditions (e. g. strictures, fistulas, leaks, and perforations). Fully covered SEMS (FSEMS) were introduced to avoid undesirable consequences of partially covered SEMS (PSEMS), but come with higher risk of stent migration. Endoscopic suturing (ES) for stent fixation has been shown to reduce migration of FSEMS. Our aim was to compare the outcomes of FSEMS with ES (FS/ES) versus PSEMS in patients with benign upper gastrointestinal conditions. PATIENTS AND METHODS: We retrospectively identified all patients who underwent stent placement for benign gastrointestinal conditions at seven US tertiary-care centers. Patients were divided into two groups: FSEMS with ES (FS/ES group) and PSEMS (PSEMS group). Clinical outcomes between the two groups were compared. RESULTS: A total of 74 (FS/ES 46, PSEMS 28) patients were included. On multivariable analysis, there was no significant difference in rate of stent migration between FS/ES (43 %) and PSEMS (15 %) (adjusted odds ratio 0.56; 95 % CI 0.15 - 2.00). Clinical success was similar [68 % vs. 64 %; P  = 0.81]. Rate of adverse events (AEs) was higher in PSEMS group [13 (46 %) vs. 10 (21 %); P  = 0.03). Difficult stent removal was higher in the PSEMS group (n = 5;17 %) vs. 0 % in the FS/ES group; P  = 0.005. CONCLUSIONS: The proportion of stent migration of FS/ES and PSEMS are similar. Rates of other stent-related AEs were higher in the PSEMS group. PSEMS was associated with tissue ingrowth or overgrowth leading to difficult stent removal, and secondary stricture formation. Thus, FSEMS with ES for stent fixation may be the preferred modality over PSEMS for the treatment of benign upper gastrointestinal conditions.

What works in implementation of integrated care programs for older adults with complex needs? A realist review.

PURPOSE: A realist review of the evaluative evidence was conducted on integrated care (IC) programs for older adults to identify key processes that lead to the success or failure of these programs in achieving outcomes such as reduced healthcare utilization, improved patient health, and improved patient and caregiver experience. DATA SOURCES: International academic literature was searched in 12 indexed, electronic databases and gray literature through internet searches, to identify evaluative studies. STUDY SELECTION: Inclusion criteria included evaluative literature on integrated, long-stay health and social care programs, published between January 1980 and July 2015, in English. DATA EXTRACTION: Data were extracted on the study purpose, period, setting, design, population, sample size, outcomes, and study results, as well as explanations of mechanisms and contextual factors influencing outcomes. RESULTS OF DATA SYNTHESIS: A total of 65 articles, representing 28 IC programs, were included in the review. Two context-mechanism-outcome configurations (CMOcs) were identified: (i) trusting multidisciplinary team relationships and (ii) provider commitment to and understanding of the model. Contextual factors such as strong leadership that sets clear goals and establishes an organizational culture in support of the program, along with joint governance structures, supported team collaboration and subsequent successful implementation. Furthermore, time to build an infrastructure to implement and flexibility in implementation, emerged as key processes instrumental to success of these programs. CONCLUSIONS: This review included a wide range of international evidence, and identified key processes for successful implementation of IC programs that should be considered by program planners, leaders and evaluators.

Evolutionary conservation and expression of miR-10a-3p in olive flounder and rock bream.

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that mainly bind to the seed sequences located within the 3' untranslated region (3' UTR) of target genes. They perform an important biological function as regulators of gene expression. Different genes can be regulated by the same miRNA, whilst different miRNAs can be regulated by the same genes. Here, the evolutionary conservation and expression pattern of miR-10a-3p in olive flounder and rock bream was examined. Binding sites (AAAUUC) to seed region of the 3' UTR of target genes were highly conserved in various species. The expression pattern of miR-10a-3p was ubiquitous in the examined tissues, whilst its expression level was decreased in gill tissues infected by viral hemorrhagic septicemia virus (VHSV) compared to the normal control. In the case of rock bream, the spleen, kidney, and liver tissues showed dominant expression levels of miR-10a-3p. Only the liver tissues in the rock bream samples infected by the iridovirus indicated a dominant miR-10a-3p expression. The gene ontology (GO) analysis of predicted target genes for miR-10a-3p revealed that multiple genes are related to binding activity, catalytic activity, cell components as well as cellular and metabolic process. Overall the results imply that the miR-10a-3p could be used as a biomarker to detect VHSV infection in olive flounder and iridovirus infection in rock bream. In addition, the data provides fundamental information for further study of the complex interaction between miR-10a-3p and gene expression.