Ependymal cells: roles in central nervous system infections and therapeutic application.

Ependymal cells are arranged along the inner surfaces of the ventricles and the central canal of the spinal cord, providing anatomical, physiological and immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found that alterations in gene expression, cell junctions, cytokine secretion and metabolic disturbances can lead to dysfunction of ependymal cells, thereby participating in the onset and progression of central nervous system (CNS) infections. Additionally, ependymal cells can exhibit proliferative and regenerative potential as well as secretory functions during CNS injury, contributing to neuroprotection and post-injury recovery. Currently, studies on ependymal cell primarily focus on the basic investigations of their morphology, function and gene expression; however, there is a notable lack of clinical translational studies examining the molecular mechanisms by which ependymal cells are involved in disease onset and progression. This limits our understanding of ependymal cells in CNS infections and the development of therapeutic applications. Therefore, this review will discuss the molecular mechanism underlying the involvement of ependymal cells in CNS infections, and explore their potential for application in clinical treatment modalities.

Systematic perturbation screens identify regulators of inflammatory macrophage states and a role for TNF mRNA m6A modification.

Macrophages exhibit remarkable functional plasticity, a requirement for their central role in tissue homeostasis. During chronic inflammation, macrophages acquire sustained inflammatory 'states' that contribute to disease, but there is limited understanding of the regulatory mechanisms that drive their generation. Here we describe a systematic functional genomics approach that combines genome-wide phenotypic screening in primary murine macrophages with transcriptional and cytokine profiling of genetic perturbations in primary human macrophages to uncover regulatory circuits of inflammatory states. This process identifies regulators of five distinct states associated with key features of macrophage function. Among these regulators, loss of the N6-methyladenosine (m6A) writer components abolishes m6A modification of TNF transcripts, thereby enhancing mRNA stability and TNF production associated with multiple inflammatory pathologies. Thus, phenotypic characterization of primary murine and human macrophages describes the regulatory circuits underlying distinct inflammatory states, revealing post-transcriptional control of TNF mRNA stability as an immunosuppressive mechanism in innate immunity.

Barriers and facilitators to the formation of professional identity among nursing students: A four-year longitudinal qualitative study.

BACKGROUND: Nursing professional identity (NPI) is essential for nurses to develop their nursing profession. It reflects the competencies consistent with the professional practices of nurses and contributes to them providing better healthcare and public health. The formation process of NPI started with undergraduate nursing education and continued throughout the nursing career. OBJECTIVE: To explore nursing students' perceptions of facilitators and barriers to the formation of NPI during their study. METHODS: A 4-year longitudinal, qualitative research design with yearly semi-structured interviews undertaken from 2019 to 2022. The reflexive thematic analysis methodology was applied for the data analysis. RESULTS: Ninety-three nursing students were recruited, joining a group or individual interview. The four-year nursing baccalaureate program revealed a dynamic formation process of NPI: "Outsider of nursing", "Entering the nursing courses", "Building nursing competence", and "Thinking and acting like a nurse". A total of 12 themes were identified to present the barriers and facilitators to the NPI formation at different stages. Specifically, the six barriers include conflict between their ideals and reality, sociocultural stereotypes about nursing, the negative impact of COVID-19, the pre-internship concerns, struggling to meet expectations, and potential danger and discrimination in the healthcare settings. The enablers were: self-motivation and inner belief towards the nursing profession, the power of role models, the improvement of nursing capacity, well integration into the healthcare professional teams, understanding of the clinical environment, and recognition and encouragement from others. CONCLUSIONS: The formation of nursing students' NPI is an ever-changing process, with various intrinsic and extrinsic influences during their four-year study. Nursing educators are suggested to prepare and develop students' professional comportment in their theoretical and clinical practice to develop their professional identity as a nurse.

Cerebral furin deficiency causes hydrocephalus in mice.

Furin is a pro-protein convertase that moves between the trans-Golgi network and cell surface in the secretory pathway. We have previously reported that cerebral overexpression of furin promotes cognitive functions in mice. Here, by generating the brain-specific furin conditional knockout (cKO) mice, we investigated the role of furin in brain development. We found that furin deficiency caused early death and growth retardation. Magnetic resonance imaging showed severe hydrocephalus. In the brain of furin cKO mice, impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expression of RAB28, a ciliary vesicle protein. In line with the widespread neuronal loss, ependymal cell layers were damaged. Further proteomics analysis revealed that cell adhesion molecules including astrocyte-enriched ITGB8 and BCAR1 were altered in furin cKO mice; and astrocyte overgrowth was accompanied by the reduced expression of SOX9, indicating a disrupted differentiation into ependymal cells. Together, whereas alteration of RAB28 expression correlated with the role of vesicle trafficking in ciliogenesis, dysfunctional astrocytes might be involved in ependymal damage contributing to hydrocephalus in furin cKO mice. The structural and molecular alterations provided a clue for further studying the potential mechanisms of furin.

Characteristics and Prevalence of Staphyloma Edges at Different Ages in Highly Myopic Eyes.

Purpose: The purpose of this study was to determine the characteristics of staphyloma edges in highly myopic eyes and how they progress. Methods: We conducted a cross-sectional analysis using baseline data and a longitudinal study with follow-up data from 256 patients (447 eyes) with high myopia, with a mean (SD) follow-up of 3.79 (0.78) years. Participants were divided into four age groups: children (<13), youth (13-24), mature (25-59), and elderly (>60). Ultrawide-field swept-source optical coherence tomography was used to analyze staphyloma edges, which were divided into four areas: nasal to the optic disc (OD), superior to the macula, inferior to the macula, and temporal to the macula. Results: Staphylomas were significantly more prevalent in the mature (42.49%) and the elderly (51.35%) groups than in the children (13%) and youth (9%) groups. Staphyloma edges were predominantly superior to the macula in the mature and elderly groups. In contrast, staphylomas were rare in children and youth, with their edges mainly located nasal to the OD. The edges of staphylomas located superior and temporal to the macula were more likely to be associated with myopic traction maculopathy. During the follow-up period, 11 new staphyloma edges developed primarily in the mature group (64%). Additionally, 12 edges had an increased degree of protrusion over time, with most cases occurring in the mature (75%) group. Conclusions: The prevalence and location of staphyloma edges show significant variations depending on age. As time progresses, staphyloma edges manifest at distinct sites and increase their protrusion, potentially playing a role in the emergence of fundus complications.

Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes.

Genetic studies have associated thousands of enhancers with breast cancer. However, the vast majority have not been functionally characterized. Thus, it remains unclear how variant-associated enhancers contribute to cancer. Here, we perform single-cell CRISPRi screens of 3,512 regulatory elements associated with breast cancer to measure the impact of these regions on transcriptional phenotypes. Analysis of >500,000 single-cell transcriptomes in two breast cancer cell lines shows that perturbation of variant-associated enhancers disrupts breast cancer gene programs. We observe variant-associated enhancers that directly or indirectly regulate the expression of cancer genes. We also find one-to-multiple and multiple-to-one network motifs where enhancers indirectly regulate cancer genes. Notably, multiple variant-associated enhancers indirectly regulate TP53. Comparative studies illustrate sub-type specific functions between enhancers in ER+ and ER- cells. Finally, we developed the pySpade package to facilitate analysis of single-cell enhancer screens. Overall, we demonstrate that enhancers form regulatory networks that link cancer genes in the genome, providing a more comprehensive understanding of the contribution of enhancers to breast cancer development.

Research trends and hotspots regarding treatment of obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is a type of sleep-disordered breathing disease, with high prevalence and multiple complications. It seriously affects patients' quality of life and even threatens their lives. Early and effective treatment can significantly improve patients' health conditions. Objective: In this study, the main treatment methods, research hotspots and trends of OSA were summarized through bibliometric and visualization analysis. Methods: From the Web of Science Core Collection database, articles on the treatment of OSA from 1999 to 2022 were obtained. CiteSpace and VOSviewer were comprehensively used to visualization of journals, co-authorship of countries, institutions and authors, co-citation of references, keywords cluster and burst. Results: A total of 2,874 publications were obtained, of which 2,584 were concerned adults and 290 about children. In adults' research, Sleep and Breathing is the most published journal (280, 10.84%), the largest number of publications come from the United States (636,24.61%) and the University of Sydney (88, 3.41%), and Pepin JL is the most published author (48, 18.58%). In children's studies, International Journal of Pediatric Otorhinolaryngology is the most published journal (41, 14.14%), the maximum number of publications were also from the United States (123, 42.41%), with the University of Pennsylvania (20, 6.90%) and Marcus CL (15, 5.17%) being the most published institutions and authors. High-frequency keywords for adults' researches include positive airway pressure, oral appliance, surgery and positional therapy. On these basis, children's studies also focus on myofunctional therapy, rapid maxillary expansion and hypoglossal nerve Stimulation. Conclusion: Over the past two decades, research in the field of OSA therapeutics has experienced significant growth in depth and breadth. The author cooperation network has already established a solid foundation, while there is potential for further strengthening the cooperation network between countries and institutions. Currently, positive airway pressure and surgery are the primary treatments for OSA in adults and children. Future research will focus on multidisciplinary combination targeted therapy, which presents a key area of interest and challenge.

Machine Learning Models for Predicting Long-Term Visual Acuity in Highly Myopic Eyes.

Importance: High myopia is a global concern due to its escalating prevalence and the potential risk of severe visual impairment caused by pathologic myopia. Using artificial intelligence to estimate future visual acuity (VA) could help clinicians to identify and monitor patients with a high risk of vision reduction in advance. Objective: To develop machine learning models to predict VA at 3 and 5 years in patients with high myopia. Design, Setting, and Participants: This retrospective, single-center, cohort study was performed on patients whose best-corrected VA (BCVA) at 3 and 5 years was known. The ophthalmic examinations of these patients were performed between October 2011 and May 2021. Thirty-four variables, including general information, basic ophthalmic information, and categories of myopic maculopathy based on fundus and optical coherence tomography images, were collected from the medical records for analysis. Main Outcomes and Measures: Regression models were developed to predict BCVA at 3 and 5 years, and a binary classification model was developed to predict the risk of developing visual impairment at 5 years. The performance of models was evaluated by discrimination metrics, calibration belts, and decision curve analysis. The importance of relative variables was assessed by explainable artificial intelligence techniques. Results: A total of 1616 eyes from 967 patients (mean [SD] age, 58.5 [14.0] years; 678 female [70.1%]) were included in this analysis. Findings showed that support vector machines presented the best prediction of BCVA at 3 years (R2 = 0.682; 95% CI, 0.625-0.733) and random forest at 5 years (R2 = 0.660; 95% CI, 0.604-0.710). To predict the risk of visual impairment at 5 years, logistic regression presented the best performance (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.816-0.912). The baseline BCVA (logMAR odds ratio [OR], 0.298; 95% CI, 0.235-0.378; P < .001), prior myopic macular neovascularization (OR, 3.290; 95% CI, 2.209-4.899; P < .001), age (OR, 1.578; 95% CI, 1.227-2.028; P < .001), and category 4 myopic maculopathy (OR, 4.899; 95% CI, 1.431-16.769; P = .01) were the 4 most important predicting variables and associated with increased risk of visual impairment at 5 years. Conclusions and Relevance: Study results suggest that developing models for accurate prediction of the long-term VA for highly myopic eyes based on clinical and imaging information is feasible. Such models could be used for the clinical assessments of future visual acuity.

Prevalence of burnout and mental health problems among medical staff during the COVID-19 pandemic: a systematic review and meta-analysis.

OBJECTIVE: The COVID-19 pandemic has had a significant impact on the burnout and mental health of medical staff. This meta-analysis aims to provide additional (and updated) evidence related to burnout and mental health problems among medical staff using a broader data pool. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library, CNKI, Wanfang data and three preprint databases (SSRN, bioRxiv and medRxiv) were searched from 1 January 2020 to 17 May 2021. ELIGIBILITY CRITERIA: We included observational studies investigating the prevalence of burnout and mental health problems among medical staff during the COVID-19 pandemic, including cross-sectional study, cohort study and case-control study. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers used a self-designed form to extract the primary data. The Joanna Briggs Institute quality appraisal tool was used to assess the quality of selected studies. Heterogeneity among studies was assessed by I2 statistic. A random-effects model was used to pool the prevalence. Subgroup analysis was performed to explore between-group differences. RESULTS: 250 studies were included, with a sample of 292 230 participants from 46 countries. The pooled prevalence of burnout, anxiety, depression, insomnia, stress, post-traumatic stress disorder symptoms and somatic symptoms was 43.6% (95% CI 36.3% to 51.2%), 37.1% (95% CI 34.7% to 39.7%), 37.6% (95% CI 35.0% to 40.4%), 43.7% (95% CI 39.1% to 48.5%), 41.3% (95% CI 35.1% to 47.9%), 30.6% (95% CI 23.6% to 38.5%) and 25.0% (95% CI 16.7% to 35.6%), respectively. Subgroup analysis showed a higher prevalence of anxiety, depression and insomnia in frontline workers than in non-frontline workers, and a higher prevalence of anxiety in females than males. Mild cases accounted for the most significant proportion of the outcomes except for stress. CONCLUSIONS: This study highlights that identifying the risks of burnout and mental health problems and adopting preventive interventions are priorities for policymakers and medical staff to avoid long-term occupational, health and social impacts. PROSPERO REGISTRATION NUMBER: CRD42021254425.

MORPHOLOGIC CHARACTERISTICS AND PROGRESSION PATTERNS OF MACULAR NEOVASCULARIZATION-RELATED ATROPHY IN EYES WITH PATHOLOGIC MYOPIA.

PURPOSE: To investigate the development and progression patterns of macular neovascularization (MNV)-related atrophies in eyes with pathologic myopia. METHODS: Twenty-seven eyes of 26 patients with MNV followed from its onset to progression to macular atrophy were studied. A longitudinal series of autofluorescence and optical coherence tomography images were examined for the patterns of MNV-related atrophy. Changes in best-corrected visual acuity were determined for each pattern. RESULTS: The mean age was 67.2 ± 8.7 years. The mean axial length was 29.6 ± 1.5 mm. Three patterns of atrophy were identified: multiple-atrophic pattern, 63% of the eyes had small atrophies occurring at multiple sites around the MNV edge; single-atrophic pattern, 18.5% had atrophies occurring only on one side of the MNV edge; and exudation-related pattern, 18.5% had atrophy occurring within a previous serous exudation or hemorrhagic area and slightly away from the MNV edge. Eyes with atrophies in multiple-atrophic and exudation-related patterns progressed to large macular atrophies involving the central fovea and showed decrease in best-corrected visual acuity during the 3-year follow-up period. Eyes with single-atrophic pattern had a sparing of the fovea and had good recovery of the best-corrected visual acuity. CONCLUSION: There are three patterns of MNV-related atrophy in eyes with pathologic myopia with different courses of progression.

DEAD-Box Helicase 17 Promotes Amyloidogenesis by Regulating BACE1 Translation.

Amyloidogenesis is one of the key pathophysiological changes in Alzheimer's disease (AD). Accumulation of the toxic Aß results from the catalytic processing of ß-amyloid precursor protein (APP) associated ß-amyloid converting enzyme 1 (BACE1) activity. It is reported that dead-box helicase 17 (DDX17) controls RNA metabolism and is involved in the development of multiple diseases. However, whether DDX17 might play a role in amyloidogenesis has not been documented. In the present study, we found that DDX17 protein level was significantly increased in HEK and SH-SY5Y cells that stably express full-length APP (HEK-APP and Y5Y-APP) and in the brain of APP/PS1 mice, an animal model of AD. DDX17 knockdown, as opposed to DDX17 overexpression, markedly reduced the protein levels of BACE1 and the ß-amyloid peptide (Aß) in Y5Y-APP cells. We further found that DDX17-mediated enhancement of BACE1 was selectively attenuated by translation inhibitors. Specifically, DDX17 selectively interacted with the 5' untranslated region (5'UTR) of BACE1 mRNA, and deletion of the 5'UTR abolished the effect of DDX17 on luciferase activity or protein level of BACE1. Here, we show that the enhanced expression of DDX17 in AD was associated with amyloidogenesis; through the 5'UTR-dependent BACE1 translation, DDX17 might serve as an important mediator contributing to the progression of AD.

The Effects of Orofacial Myofunctional Therapy on Children with OSAHS's Craniomaxillofacial Growth: A Systematic Review.

Orofacial myofunctional therapy (OMT) is one of the therapeutic methods for neuromuscular re-education and has been considered as one of the auxiliary methods for obstructive sleep apnea hypopnea syndrome (OSAHS) and orthodontic treatment. There is a dearth of comprehensive analysis of OMT's effects on muscle morphology and function. This systematic review examines the literature on the craniomaxillofacial effects of OMT in children with OSAHS. This systematic analysis was carried out using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards, and the research was scanned using PICO principles. A total of 1776 articles were retrieved within a limited time, with 146 papers accepted for full-text perusing following preliminary inspection and 9 of those ultimately included in the qualitative analysis. Three studies were rated as having a severe bias risk, and five studies were rated as having a moderate bias risk. Improvement in craniofacial function or morphology was observed in most of the 693 children. OMT can improve the function or morphology of the craniofacial surface of children with OSAHS, and its effect becomes more significant as the duration of the intervention increases and compliance improves. In the majority of the 693 infants, improvements in craniofacial function or morphology were seen. The function or morphology of a kid's craniofacial surface can be improved with OMT, and as the duration of the intervention lengthens and compliance rises, the impact becomes more pronounced.

CHD-associated enhancers shape human cardiomyocyte lineage commitment.

Enhancers orchestrate gene expression programs that drive multicellular development and lineage commitment. Thus, genetic variants at enhancers are thought to contribute to developmental diseases by altering cell fate commitment. However, while many variant-containing enhancers have been identified, studies to endogenously test the impact of these enhancers on lineage commitment have been lacking. We perform a single-cell CRISPRi screen to assess the endogenous roles of 25 enhancers and putative cardiac target genes implicated in genetic studies of congenital heart defects (CHDs). We identify 16 enhancers whose repression leads to deficient differentiation of human cardiomyocytes (CMs). A focused CRISPRi validation screen shows that repression of TBX5 enhancers delays the transcriptional switch from mid- to late-stage CM states. Endogenous genetic deletions of two TBX5 enhancers phenocopy epigenetic perturbations. Together, these results identify critical enhancers of cardiac development and suggest that misregulation of these enhancers could contribute to cardiac defects in human patients.

Vitamin C promoted refractory organic contaminant elimination in the zero-valent iron/peracetic acid system: Efficiency, mechanism and effects of various parameters.

The conventional zero-valent iron/peracetic acid (ZVI/PAA) system is severely limited owing to the passivation of ZVI and the low recovery of Fe2+. In this study, a reducing agent, vitamin C (H2A), was used for the first time to enhance the ZVI/PAA system as a way to improve its degradation performance. Under optimal conditions, the removal efficiency of the H2A/ZVI/PAA system was 82.9%, while that of the H2A/PAA and ZVI/PAA systems were only 19.0% and 25.6%. Free radical quenching and electron paramagnetic experiments (EPR) confirmed that CH3C(O)O•, •OH and CH3C(O)OO• were the major active species for acid orange 7 (AO7) degradation with contributions of 9.7%, 75% and 14.4%, respectively. The degradation mechanism was proposed through UV-vis full-wavelength scanning and chemical oxygen demand (COD) experiments. The removal of AO7 was not affected in the presence of Cl-, SO42- and HCO3-, while inhibition occurred with humic acid. ZVI exhibited excellent catalytic properties and stability, and the removal efficiency of AO7 exceeded 70% after three cycles. Additionally, the H2A/ZVI/PAA system showed good ability to remove AO7 in well water, lake water, river water and reservoir water, and the elimination efficiency of MO, DCF and ACE also exceeded 70%. Overall, this study contributes new cognition for enhancing the ZVI/PAA system to degrade contaminants, which is expected to achieve a cleaner water environment.

LONGITUDINAL STUDY OF CHANGES IN INNER SCLERAL CURVATURE PATTERNS AND DEVELOPMENT OF POSTERIOR STAPHYLOMAS IN HIGHLY MYOPIC EYES OF CHILDREN AND ADOLESCENTS.

PURPOSE: To determine the longitudinal changes in patterns of inner scleral curvature and development of posterior staphylomas in the eyes of highly myopic youths. METHODS: A retrospective, longitudinal study. Ultra-widefield optic coherence tomographic (UWF-OCT) images from 47 eyes of 24 highly myopic patients with a follow-up period of 2 to 4 years were analyzed. Patients were divided into two groups, the children group younger than 10 years and the adolescents group aged 11 to 19 years. RESULTS: During the follow-up period, the scleral curvature patterns changed in either the horizontal or vertical optical coherence tomographic sections in 27 of the 46 eyes (58.7%) of both groups. The changes were significantly more frequent in children than adolescents. The change in the vertical section from symmetrical to asymmetrical in almost of children was correlated with an increase in the axial length and myopia. Four eyes had a staphyloma at the baseline. The staphyloma developed in six eyes of the remaining 43 eyes (14%). All staphyloma edges were found at or around the optic disc and were oriented in the horizontal direction. CONCLUSION: Our results showed that UWF-OCT images can be used to determine the process of new staphyloma formation and concurrent changes in scleral curvature patterns.

COMPLEX HEMODYNAMICS OF INTERVORTEX VEIN ANASTOMOSES IN HIGHLY MYOPIC EYES.

PURPOSE: To analyze the complex pattern of filling of the intervortex vein (IVV) anastomoses through large trunks in highly myopic eyes based on indocyanine green angiographic (ICGA) videos. METHODS: The medical records of 1,060 consecutive highly myopic eyes that had undergone ICGA were studied. IVV anastomoses were identified in the ICGA images, and the ICGA images and videos were analyzed comprehensively to characterize their hemodynamic features. RESULTS: Seven eyes with IVV anastomoses through large trunks were analyzed. In the ICGA videos of six eyes, laminar flow was observed in the IVV anastomotic vessels. The laminar flow started in the arterial phase in two eyes, with pulsatile fashion in 1 of them. The flow began in the early arteriovenous transition phase in four eyes. The laminar flow continued for a mean of 12.17 ± 3.06 seconds, and the remaining section was gradually filled slower than the surrounding veins. The anastomotic trunk for the remaining one eye was too narrow to be analyzed. Four eyes had longitudinal ICGA records, and two had significant attenuation and narrowing of the anastomotic vessels. CONCLUSION: The very early filling of part of the IVV anastomoses suggests that arteriovenous anastomoses are involved in the IVV of highly myopic eyes. However, this suggestion needs further study. There may be similar pathogenesis for IVV anastomoses either in thick or thin sclera.

Apicidin attenuates memory deficits by reducing the Aß load in APP/PS1 mice.

AIMS: Amyloid beta (Aß) is an important pathological feature of Alzheimer's disease (AD). A disintegrin and metalloproteinase 10 (ADAM10) can reduce the production of toxic Aß by activating the nonamyloidogenic pathway of amyloid precursor protein (APP). We previously found that apicidin, which is a histone deacetylase (HDAC) inhibitor, can promote the expression of ADAM10 and reduce the production of Aß in vitro. This study was designed to determine the potential of apicidin treatment to reverse learning and memory impairments in an AD mouse model and the possible correlation of these effects with ADAM10. METHODS: Nine-month-old APP/PS1 mice and C57 mice received intraperitoneal injections of apicidin or vehicle for 2 months. At 11 months of age, we evaluated the memory performance of mice with Morris water maze (MWM) and context fear conditioning tests. The Aß levels were assessed in mouse brain using the immunohistochemical method and ELISA. The expression of corresponding protein involved in proteolytic processing of APP and the phosphorylation of tau were assessed by Western blotting. RESULTS: Apicidin reversed the deficits of spatial reference memory and contextual fear memory, attenuated the formation of Aß-enriched plaques, and decreased the levels of soluble and insoluble Aß40/42 in APP/PS1 mice. Moreover, apicidin significantly increased the expression of ADAM10, improved the level of sAPPα, and reduced the production of sAPPß, but did not affect the levels of phosphorylated tau in APP/PS1 mice. CONCLUSION: Apicidin significantly improves the AD symptoms of APP/PS1 mice by regulating the expression of ADAM10, which may contribute to decreasing the levels of Aß rather than decreasing the phosphorylation of tau.

Stroke survivors', caregivers' and nurse coaches' perspectives on health coaching program towards hospital-to-home transition care: A qualitative descriptive process evaluation.

AIMS AND OBJECTIVES: To explore the perspectives of stroke survivors, caregivers and nurse coaches on a health coaching program during hospital-to-home transitional care. BACKGROUND: Stroke is a major public health problem that seriously affects the health and safety of people in China. Nurse-led health coaching is a promising support option in enabling smooth hospital-to-home transition for stroke survivors and family caregivers. A qualitative study is valuable for gaining insight into their perspectives on using this program. DESIGN: An exploratory, descriptive qualitative process evaluation was conducted parallel with a former randomised controlled trial. Data were obtained from 26 stroke survivors, 33 caregivers and four nurse coaches with semi-structured interviews. The inductive reflexive thematic analysis approach was used for data analysis. The COREQ checklist was followed in reporting this study. RESULTS: Seven themes were generated from the data: (1) the applicability of individualised health coaching sessions, (2) driving self-efficacy to establish self-care skills, (3) the key role of nurse coaches, (4) coordination among healthcare teams during the transition, (5) adequate community and social support, (6) insufficient rehabilitative services after discharge and (7) perceived extra workload for nurse coaches. CONCLUSIONS: The study captured perspectives on a nurse-led health coaching program towards hospital-to-home transition care from stroke survivors, caregivers and nurse coaches. Individualised health coaching sessions and driving self-efficacy were perceived as facilitators for empowering the self-care skills of stroke survivors and caregivers. The key role of nurse coaches in coordinating healthcare teams and adequate community and social support were detected as the power frame of the program's implementation. However, health system obstacles, such as insufficient rehabilitative services and the high workload of nurses, still need to be addressed to ensure the sustainability of health coaching intervention in transitional care. RELEVANCE TO CLINICAL PRACTICE: The study suggested the feasibility of implementing nurse-led health coaching to smooth post-stroke hospital-to-home transitional care. The findings also highlighted the importance of qualitative process evaluation when implementing evidence-based interventions in health care. TRIAL REGISTRATION: The trial was registered with the Australia New Zealand Clinical Trials Registry (ID: ACTRN12619000321145).

AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.

AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic ß-amyloid peptide (Aß). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aß in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aß, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.

Papillary and Peripapillary Hemorrhages in Eyes With Pathologic Myopia.

Purpose: To determine the prevalence, characteristics, and causes of papillary and peripapillary hemorrhages (PPHs) in eyes with pathologic myopia (PM). Methods: PM patients were retrospectively studied between 2011 and 2018. Fundus images were used to diagnose and classify the PPHs. Fundus fluorescein angiographic (FFA) and optical coherence tomographic (OCT) images were used to determine the status of the retinal vessels and tissue at and around the PPH sites. Visual field data determined by Goldmann perimetry and Humphrey visual field analyzer were also analyzed. Results: A total of 2171 PM patients (3774 eyes) were examined. Eighty-eight patients (97 eyes) had PPHs (mean age 66.8 ± 11.9 years; mean axial length 30.79 ± 2.17 mm) for a prevalence of 4.05%. Thirty (30.9%) eyes recurred. Among the 90 eyes with a single-site PPH, the most common type and location were the conus type (49 eyes, 54.4%) and the temporal side (66 eyes, 73.3%), respectively. Regression analysis showed that patchy atrophy reduced the risk of recurrences than diffuse atrophy (P < 0.05), whereas a longer axial length and potential glaucoma increased the risk (both P < 0.05). FFA and OCT showed that PPHs developed in the area of straightened retinal arterioles (24 eyes), at or beside the peak of a ridge (10 eyes), in an area of compressed retinal tissue (two eyes). Conclusions: PPHs are present in 4.05% of PM eyes, and they are most often located in the temporal peripapillary atrophic region of the retina. Axial elongation, mild myopic maculopathy, and potential glaucoma are risk factors for recurrences.