Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat in the Huntingtin (HTT) gene, encoding a homopolymeric polyglutamine (polyQ) tract. Although mutant HTT (mHTT) protein is known to aggregate, the links between aggregation and neurotoxicity remain unclear. Here we show that both translation and aggregation of wild-type HTT and mHTT are regulated by a stress-responsive upstream open reading frame and that polyQ expansions cause abortive translation termination and release of truncated, aggregation-prone mHTT fragments. Notably, we find that mHTT depletes translation elongation factor eIF5A in brains of symptomatic HD mice and cultured HD cells, leading to pervasive ribosome pausing and collisions. Loss of eIF5A disrupts homeostatic controls and impairs recovery from acute stress. Importantly, drugs that inhibit translation initiation reduce premature termination and mitigate this escalating cascade of ribotoxic stress and dysfunction in HD.

Exploring the Effectiveness of Nurses' Usage of a Wound-Photography System.

As a result of rapid advancements in health information technology, uploading health-related information and records onto an electronic health record system has become a common practice. Photographs of patients' wounds have been uploaded electronically, but widespread acceptance by nurses has been prevented owing to issues such as file size and equipment. This research explores the attitude and satisfaction toward using an electronic health record for uploading wound photos. Through the integration of the Technology Acceptance Model, Information System Success Model, and other study results, this research aims to explore the impact of the following variables: system quality, information quality, perceived usefulness, perceived ease of use, user attitude, user satisfaction, and net benefits. We also tested nurses' understanding regarding the process of taking photographs and explored the photograph quality and the photography uploading rates. The results revealed that users were satisfied with the wound-photography system, but some believed that the system stability, processing time, and image resolution should be improved. In addition, more than 80% of the nurses correctly answered photo-taking questions, the study photos reached 70% of the quality standards, and the average uploading rate was 74%. The results could serve as guidelines for system design in the future.

Exploring the Usage Effectiveness of a Nursing Charge System.

The nursing charge system for inpatient accounting has been utilized in healthcare institutions for years. However, the level of its effectiveness in meeting the needs of nursing services, including further development, has not been systematically evaluated. A cross-sectional study based in Delone and McLean's information system success model was applied to explore the level of effective nursing charge system usage across the five dimensions of system quality, information quality, service quality, user satisfaction, and net benefits. We conducted a survey of the inpatient units of a medical center in Taiwan from June 23, 2021, to July 23, 2021. A total of 214 valid questionnaires were collected. Using a 5-point Likert scale, the dimension with the highest score was information quality (3.71), followed by service quality (3.37), user satisfaction (3.36), net benefits (3.31), and system quality (3.23). Older nurses (r = -0.176) and those with more clinical experience (r = -0.151) viewed the nursing charge system as having less information quality. The comfort level with using the computer was positively associated with system quality (r = 0.396), information quality (r = 0.378), service quality (r = 0.275), user satisfaction (r = 0.417), and net benefits (r = 0.355). The opinions of nurses are vital. User feedback and advice should be investigated regularly to achieve system optimization.

Factors Related to Family Caregivers' Readiness for the Hospital Discharge of Advanced Cancer Patients.

Background: Many family caregivers of advanced cancer patients worry about being unable to provide in-home care and delay the discharge. Little is known about the influencing factors of discharge readiness. Methods: This study aimed to investigate the influencing factors of family caregivers' readiness, used a cross-sectional survey, and enrolled 123 sets of advanced cancer patients and family caregivers using convenience sampling from four oncology wards in a medical centre in northern Taiwan. A self-developed five-point Likert questionnaire, the "Discharge Care Assessment Scale", surveyed the family caregivers' difficulties with providing in-home care. Results: The study showed that the discharge readiness of family caregivers affects whether patients can be discharged home. Moreover, the influencing factors of family caregivers' discharge readiness were the patient's physical activity performance status and expressed discharge willingness; the presence of someone to assist family caregivers with in-home care; and the difficulties of in-home care. The best prediction model accuracy was78.0%, and the Nagelkerke R2 was 0.52. Conclusion: Discharge planning should start at the point of admission data collection, with the influencing factors of family caregivers' discharge readiness. It is essential to help patients increase the likelihood of being discharged home.

Critical Care Nurses' Perceptions of Clinical Alarm Management on Nursing Practice.

The alarm management of physiological monitoring systems is a key responsibility of critical care nurses. However, the high numbers of false and nonactionable (true but clinically irrelevant) alarms cause distractions to healthcare professionals, interruptions to nursing workflow, and ignoring of crucial tasks. Therefore, understanding how nurses manage large amounts of alarms in their daily work could provide a direction to design interventions to prevent adverse patient care effects. A qualitative design with focus group interviews was conducted with 37 nurses in Taiwan. Content analysis was performed to analyze the interview data, and four main themes were derived: (1) the foundation stone of critical care nursing practice; (2) a trajectory adaptation of alarms management; (3) adverse impacts on the quality of care and patient safety; and (4) a hope for multimodal learning alternatives and wireless technology. Nurses manage alarm parameter settings influenced not only by their knowledge and skills of patient care, but also in accordance with the three dimensions of technology, human, and organization evaluation framework. Customized alarm management training alternatives, patient-centered care values, and application of wireless technology are the suggested approaches to enhance nursing care and minimize the risk of adverse events.

Exploring the Outcomes and Satisfaction of Automated Physiological Monitoring Systems Among Nurses.

Vital signs are central to the assessment of physiologic functions of patients and must be included in the electronic health record. The purpose of this retrospective and cross-sectional design study was to evaluate use of-and satisfaction with-automated physiological monitoring systems. Usage data from a hospital database were analyzed 3, 6, and 12 months after implementation of the automated system (June 2018 to May 2019). In addition, questionnaires were completed by 168 nurses, and 20 nurses were interviewed between August/September 2020 and October/November 2020, respectively. Results revealed that usage frequency of automated physiological monitoring devices increased steadily with user familiarity. Although respondents indicated general satisfaction with the devices, system downtime, sufficiency of the battery charge, and data transmission speed were identified as needing correction to smooth workflow and boost work efficiency. Although most interviewees considered devices easy to use, some mentioned transmission speed of the gateway, scanner sensitivity, and accuracy of the ear thermometer as needing improvement. For nurses to use automated physiological monitoring devices fully, a user-friendly design in functions and features is vital, and in-service training and a streamlined workflow are recommended to facilitate technology adoption.

Evaluation of the Pressure Injury Prevention Information System.

Clinical decision support systems provide empirical guidance to improve the quality of nursing care. This study aimed to evaluate the outcomes of implementation of decision support functions into the preventive care system as regards nurses' acceptance of technology, documentation completeness, and incidence of hospital-acquired pressure injury. The researchers performed data collection in a regional hospital in northern Taiwan. The study used the Davis Science and Technology Acceptance Model scale to investigate nurses' technology acceptance before and after the introduction of a clinical decision support system and compared documentation compliance of preventive records with the incidence of hospital-acquired pressure injuries. Results showed that nurses' acceptance of the technology was significantly improved, and the completion rate of the pressure injury preventive care record significantly increased from 88.9% to 99.9%. Meanwhile, the incidence of hospital-acquired pressure injury decreased significantly from 0.057% to 0.021%. Therefore, it was concluded that the clinical decision support system provides evidenced-based support to nurses and is effective in identifying patient-specific prevention nursing plans of care.

Evaluation of Electronic Health Records on the Nursing Process and Patient Outcomes Regarding Fall and Pressure Injuries.

Digitalizing the nursing process has become a trend in medical care. The purpose of this study was to evaluate implementation of the Standardized Computerized Nursing Process Documentation System and patient outcomes. We analyzed hospitalized patients' electronic health record database with a total of 19 659 patients in 2015. The analysis focused on nurses' selection of nursing care plans for patients with a high risk of falls or pressure injuries through admission assessments. The effectiveness of implemented nursing care plans following falls or pressure injuries was explored. The results reveal that 55% of the hospitalized patients had a risk of falling, and 27.85% of patients were at risk of pressure injuries. Patients receiving nursing care plan who experienced falls or pressure injuries were significantly higher than those without a nursing care plan (P < .001). This study could not provide direct evidence for the effect of nursing care plans on reducing the incidence of falls and pressure injuries, which may be attributable to patient characteristics. Furthermore, an analysis on data from 2007 to 2017 using a run chart revealed that the mean incidence rate for pressure injuries decreased, whereas that for falls remained stable. The results indicate that the system did not increase the occurrence of such incidences.

The Effect of Barcode Technology Use on Pathology Specimen Labeling Errors.

Pathology specimen labeling errors occur for a variety of reasons. We investigated the use of barcode technology as a method to improve the accuracy of pathology specimen labeling and patient safety. We also assessed nurses' perceptions of system quality, information quality, service quality, user satisfaction, and net benefits. Sixty-eight perioperative nurses who work in a teaching hospital in Taiwan completed the survey. Nurses scored net benefits as highly contributing to their satisfaction, whereas system quality contributed most to dissatisfaction. Further, we analyzed pathology specimen records before and after implementing the barcode system and found that specimen management errors significantly decreased. The use of a reliable barcode system could improve specimen labeling accuracy and enhance nurses' satisfaction with this technology.

Evaluation of a Barcode Medication Administration Information System.

When a medication administration error occurs, patient safety is endangered. Barcode medication administration system usage has been implemented to reduce medication errors. The purpose of this study was to evaluate barcode medication administration system usage outcomes. A survey based on DeLone and McLean's model of information systems success was utilized. The questionnaire, composed of 27 items, explored system quality, information quality, service quality, user satisfaction, and usage benefits. It was completed by 232 nurses. User satisfaction received the highest average score, and quality of information was the most critical factor related to this result (r = 0.83, P < .01). Medication errors occurring before and after barcode medication administration use were collected, and the reasons for errors related to work process were explored. Medication errors decreased from 405 at preimplementation to 314 at postimplementation (t = 77.62, P < .001). The main reason for medication errors related to work process was "not following the standard procedure," followed by "other factors." While technology is deployed to support individual practice, organizational elements also remain important to technology adoption.

C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases.

The proteolysis-assisted protein quality control system guards the proteome from potentially detrimental aberrant proteins. How miscellaneous defective proteins are specifically eliminated and which molecular characteristics direct them for removal are fundamental questions. We reveal a mechanism, DesCEND (destruction via C-end degrons), by which CRL2 ubiquitin ligase uses interchangeable substrate receptors to recognize the unusual C termini of abnormal proteins (i.e., C-end degrons). C-end degrons are mostly less than ten residues in length and comprise a few indispensable residues along with some rather degenerate ones. The C-terminal end position is essential for C-end degron function. Truncated selenoproteins generated by translation errors and the USP1 N-terminal fragment from post-translational cleavage are eliminated by DesCEND. DesCEND also targets full-length proteins with naturally occurring C-end degrons. The C-end degron in DesCEND echoes the N-end degron in the N-end rule pathway, highlighting the dominance of protein "ends" as indicators for protein elimination.

Clustered Regularly Interspaced Short Palindromic Repeats-Based Genome Surgery for the Treatment of Autosomal Dominant Retinitis Pigmentosa.

PURPOSE: To develop a universal gene therapy to overcome the genetic heterogeneity in retinitis pigmentosa (RP) resulting from mutations in rhodopsin (RHO). DESIGN: Experimental study for a combination gene therapy that uses both gene ablation and gene replacement. PARTICIPANTS: This study included 2 kinds of human RHO mutation knock-in mouse models: RhoP23H and RhoD190N. In total, 23 RhoP23H/P23H, 43 RhoP23H/+, and 31 RhoD190N/+ mice were used for analysis. METHODS: This study involved gene therapy using dual adeno-associated viruses (AAVs) that (1) destroy expression of the endogenous Rho gene in a mutation-independent manner via an improved clustered regularly interspaced short palindromic repeats-based gene deletion and (2) enable expression of wild-type protein via exogenous cDNA. MAIN OUTCOME MEASURES: Electroretinographic and histologic analysis. RESULTS: The thickness of the outer nuclear layer (ONL) after the subretinal injection of combination ablate-and-replace gene therapy was approximately 17% to 36% more than the ONL thickness resulting from gene replacement-only therapy at 3 months after AAV injection. Furthermore, electroretinography results demonstrated that the a and b waves of both RhoP23H and RhoD190N disease models were preserved more significantly using ablate-and-replace gene therapy (P < 0.001), but not by gene replacement monotherapy. CONCLUSIONS: As a proof of concept, our results suggest that the ablate-and-replace strategy can ameliorate disease progression as measured by photoreceptor structure and function for both of the human mutation knock-in models. These results demonstrate the potency of the ablate-and-replace strategy to treat RP caused by different Rho mutations. Furthermore, because ablate-and-replace treatment is mutation independent, this strategy may be used to treat a wide array of dominant diseases in ophthalmology and other fields. Clinical trials using ablate-and-replace gene therapy would allow researchers to determine if this strategy provides any benefits for patients with diseases of interest.

Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients.

Differential expression of neuregulin-1 (NRG1) mRNA isoforms and proteins has been reported in schizophrenia, primarily in post-mortem brain tissue. In this study, we examined 12 NRG1 SNPs, eight NRG1 mRNA isoforms (type I, type I(Ig2), type II, type III, type IV, EGFα, EGFß, pan-NRG1) in whole blood, and NRG1-ß1 protein in serum of clozapine-treated schizophrenia patients (N = 71) and healthy controls (N = 57). In addition, using cultured peripheral blood mononuclear cells (PBMC) from 15 healthy individuals, we examined the effect of clozapine on NRG1 mRNA isoform and protein expression. We found elevated levels of NRG1 mRNA, specifically the EGFα (P = 0.0175), EGFß (P = 0.002) and type I(Ig2) (P = 0.023) containing transcripts, but lower NRG1-ß1 serum protein levels (P = 0.019) in schizophrenia patients compared to healthy controls. However, adjusting for smoking status attenuated the difference in NRG1-ß1 serum levels (P = 0.050). Examination of clinical factors showed NRG1 EGFα (P = 0.02) and EGFß (P = 0.02) isoform expression was negatively correlated with age of onset. However, we found limited evidence that NRG1 mRNA isoform or protein expression was associated with current chlorpromazine equivalent dose or clozapine plasma levels, the latter corroborated by our PBMC clozapine exposure experiment. Our SNP analysis found no robust expression quantitative trait loci. Our results represent the first comprehensive investigation of NRG1 isoforms and protein expression in the blood of clozapine-treated schizophrenia patients and suggest levels of some NRG1 transcripts are upregulated in those with schizophrenia.

Peripheral Transcription of NRG-ErbB Pathway Genes Are Upregulated in Treatment-Resistant Schizophrenia.

Investigation of peripheral gene expression patterns of transcripts within the NRG-ErbB signaling pathway, other than neuregulin-1 (NRG1), among patients with schizophrenia and more specifically treatment-resistant schizophrenia (TRS) is limited. The present study built on our previous work demonstrating elevated levels of NRG1 EGFα, EGFß, and type I(Ig2) containing transcripts in TRS by investigating 11 NRG-ErbB signaling pathway mRNA transcripts (NRG2, ErbB1, ErbB2, ErbB3, ErbB4, PIK3CD, PIK3R3, AKT1, mTOR, P70S6K, eIF4EBP1) in whole blood of TRS patients (N = 71) and healthy controls (N = 57). We also examined the effect of clozapine exposure on transcript levels using cultured peripheral blood mononuclear cells (PBMCs) from 15 healthy individuals. Five transcripts (ErbB3, PIK3CD, AKT1, P70S6K, eIF4EBP1) were significantly elevated in TRS patients compared to healthy controls but only expression of P70S6K (Pcorrected = 0.018), a protein kinase linked to protein synthesis, cell growth, and cell proliferation, survived correction for multiple testing using the Benjamini-Hochberg method. Investigation of clinical factors revealed that ErbB2, PIK3CD, PIK3R3, AKT1, mTOR, and P70S6K expression were negatively correlated with duration of illness. However, no transcript was associated with chlorpromazine equivalent dose or clozapine plasma levels, the latter supported by our in vitro PBMC clozapine exposure experiment. Taken together with previously published NRG1 results, our findings suggest an overall upregulation of transcripts within the NRG-ErbB signaling pathway among individuals with schizophrenia some of which attenuate over duration of illness. Follow-up studies are needed to determine if the observed peripheral upregulation of transcripts within the NRG-ErbB signaling pathway are specific to TRS or are a general blood-based marker of schizophrenia.

Experience of Home Telehealth Technology in Older Patients With Diabetes.

The incidence of diabetes, a common chronic disease among older adults, is increasing annually. The lack of blood glucose regulation can result in severe diabetes-related complications and substantial healthcare costs, making self-care programs specific to this population especially important. Combined with reduced numbers of healthcare professionals, the integration of healthcare and information technology and the older adults' adoption of telehealth services have become increasingly important. This study used a qualitative method to interview 18 older study participants who used a telehealth service. Subject perceptions and suggestions regarding using such a service for diabetes management were investigated. Content analysis was used to examine the interview data and determine the older patients' acceptance and perceived benefits of telehealth service. Four main themes emerged: (1) initial trial encouragement from the doctors, nurses, and financial incentives; (2) enhanced self-management capability through continuous device use for better outcomes; (3) ambivalent feelings regarding dependence on others for problem solving; and (4) consideration for continual technology use for an uncertain future. These results serve as a reference for promoting, assessing, and verifying telehealth models for older patients with diabetes.

CRISPR Repair Reveals Causative Mutation in a Preclinical Model of Retinitis Pigmentosa.

Massive parallel sequencing enables identification of numerous genetic variants in mutant organisms, but determining pathogenicity of any one mutation can be daunting. The most commonly studied preclinical model of retinitis pigmentosa called the "rodless" (rd1) mouse is homozygous for two mutations: a nonsense point mutation (Y347X) and an intronic insertion of a leukemia virus (Xmv-28). Distinguishing which mutation causes retinal degeneration is still under debate nearly a century after the discovery of this model organism. Here, we performed gene editing using the CRISPR/Cas9 system and demonstrated that the Y347X mutation is the causative variant of disease. Genome editing in the first generation produced animals that were mosaic for the corrected allele but still showed neurofunction preservation despite low repair frequencies. Furthermore, second-generation CRISPR-repaired mice showed an even more robust rescue and amelioration of the disease. This predicts excellent outcomes for gene editing in diseased human tissue, as Pde6b, the mutated gene in rd1 mice, has an orthologous intron-exon relationship comparable with the human PDE6B gene. Not only do these findings resolve the debate surrounding the source of neurodegeneration in the rd1 model, but they also provide the first example of homology-directed recombination-mediated gene correction in the visual system.

Nurses' Experiences of an Initial and Reimplemented Electronic Health Record Use.

The electronic health record is a key component of healthcare information systems. Currently, numerous hospitals have adopted electronic health records to replace paper-based records to document care processes and improve care quality. Integrating healthcare information system into traditional nursing daily operations requires time and effort for nurses to become familiarized with this new technology. In the stages of electronic health record implementation, smooth adoption can streamline clinical nursing activities. In order to explore the adoption process, a descriptive qualitative study design and focus group interviews were conducted 3 months after and 2 years after electronic health record system implementation (system aborted 1 year in between) in one hospital located in southern Taiwan. Content analysis was performed to analyze the interview data, and six main themes were derived, in the first stage: (1) liability, work stress, and anticipation for electronic health record; (2) slow network speed, user-unfriendly design for learning process; (3) insufficient information technology/organization support; on the second stage: (4) getting used to electronic health record and further system requirements, (5) benefits of electronic health record in time saving and documentation, (6) unrealistic information technology competence expectation and future use. It concluded that user-friendly design and support by informatics technology and manpower backup would facilitate this adoption process as well.

Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV.

This investigation aimed to assess whether inhibition of cathecol-O-methyl transferase (COMT) by tolcapone could provide neuroprotection against HIV-associated neurodegenerative effects. This study was conducted based on a previous work, which showed that a single nucleotide polymorphism (SNP) at position 158 (val158met) in COMT, resulted in 40 % lower COMT activity. Importantly, this reduction confers a protective effect against HIV-associated neurocognitive disorders (HAND), which have been linked to HIV-associated brain changes. SH-SY5Y-differentiated neurons were exposed to macrophage-propagated HIV (neurotropic MACS2-Br strain) in the presence or absence of tolcapone for 6 days. RNA was extracted, and qPCR was performed using Qiagen RT2 custom array consisting of genes for neuronal and synaptic integrity, COMT and pro-inflammatory markers. Immunofluorescence was conducted to validate the gene expression changes at the protein level. Our findings demonstrated that HIV significantly increased the messenger RNA (mRNA) expression of COMT while reducing the expression of microtubule-associated protein 2 (MAP2) (p = 0.0015) and synaptophysin (SYP) (p = 0.012) compared to control. A concomitant exposure of tolcapone ameliorated the perturbed expression of MAP2 (p = 0.009) and COMT (p = 0.024) associated with HIV. Immunofluorescence revealed a trend reduction of SYP and MAP2 with exposure to HIV and that concomitant exposure of tolcapone increased SYP (p = 0.016) compared to HIV alone. Our findings demonstrated in vitro that inhibition of COMT can ameliorate HIV-associated neurodegenerative changes that resulted in the decreased expression of the structural and synaptic components MAP2 and SYP. As HIV-associated dendritic and synaptic damage are contributors to HAND, inhibition of COMT may represent a potential strategy for attenuating or preventing some of the symptoms of HAND.

Nurses' perceptions of e-portfolio use for on-the-job training in Taiwan.

Electronic portfolios can be used to record user performance and achievements. Currently, clinical learning systems and in-service education systems lack integration of nurses' clinical performance records with their education or training outcomes. For nurses with less than 2 years' work experience (nursing postgraduate year), use of an electronic portfolio is essential. This study aimed to assess the requirements of using electronic portfolios in continuing nursing education for clinical practices. Fifteen nurses were recruited using a qualitative purposive sampling approach between April 2013 and May 2013. After obtaining participants' consent, data were collected in a conference room of the study hospital by one-on-one semistructured in-depth interviews. Through data analyses, the following five main themes related to electronic learning portfolios were identified: instant access to in-service education information, computerized nursing postgraduate year training manual, diversity of system functions and interface designs, need for sufficient computers, and protection of personal documents. Because electronic portfolios are beginning to be used in clinical settings, a well-designed education information system not only can meet the needs of nurses but also can facilitate their learning progress.

The evaluation of diabetic patients' use of a telehealth program.

Diabetes is a metabolic disorder that, if not treated promptly and appropriately, can cause complex health complications and mortality. Care models that apply technology, such as telehealth, may be useful in working with diabetes patients. The development and application of wireless communication telehealth have significantly affected healthcare in recent years. Thus, the purpose of this study was to evaluate diabetic patients' use of a telehealth program by using questionnaire survey and laboratory data results. A quantitative study, 1-group pretest-posttest design, was conducted. This study recruited 20 diabetic patients who received telehealth service to measure their glucose, heart rate, and blood pressure, with data uploaded back to the hospital daily. A questionnaire survey was conducted in May 2012 and between August and January 2013 with 20 participants. The test values (blood pressure, heart rate, and blood glucose) of subjects were obtained from the hospital telecare platform and the outpatient monthly reporting system. Study findings showed an overall satisfaction rating of 91% by telehealth participants. Nonparametric statistical analysis demonstrated a significant difference (P < .01) in participants' glycosylated hemoglobin and resultant effective control. These findings indicated that participants accepted this care model, and telehealth could improve participants' glucose control.