Discovery of an Ortho-Substituted N-Cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaine Derivative as a Selective and Potent Kappa Opioid Receptor Agonist with Subsided Sedative Effect.

Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of ortho-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound 7a exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, Ki = 3.9 nM, MOR/KOR = 270, DOR/KOR = 1075; [35S]GTPγS binding, EC50 = 3.4 nM). Additionally, this compound exhibited robust and persistent antinociceptive effects in rodent models with different animal strains (hot plate test, ED50 = 0.20-0.30 mg/kg, i.p.; abdominal constriction test, ED50 = 0.20-0.60 mg/kg, i.p.), with its KOR-mediated mechanism for antinociception firmly established. Notably, compound 7a, unlike conventional KOR agonists, displayed minimal sedation and aversion at the antinociceptive ED50 dose. This feature addresses a crucial limitation in existing KOR agonists, positioning compound 7a as a promising novel therapeutic agent.

Summary of evidence to facilitate the implementation of advance care planning among advanced cancer patients. / ä¿ƒè¿›æ™šæœŸç™Œç—‡æ‚£è€ é¢„ç«‹åŒ»ç–—ç §æŠ¤è®¡åˆ’å®žæ–½çš„è¯æ®æ€»ç»“.

Advance care planning (ACP) is designed to ensure that patients lacking autonomous decision-making capacity receive medical services in accordance with their expectations and preferences. Individuals with advanced cancer are a crucial target for ACP implementation. However, the current practice of ACP in this group in China is suboptimal, demanding high-quality implementation evidence to strengthen ACP in the clinical practice of patients with advanced cancer. The existing literature can be summarized into 27 pieces of evidence across 7 dimensions, including initiation time, intervention content, intervention providers, intervention modalities, communication skills, outcome indicators, and environmental support. The aforementioned evidence could provide crucial support for improving ACP implementation for patients with advanced cancer. Subsequent research efforts should integrate patient preferences and explore the most suitable implementation strategies for ACP in the Chinese population with advanced cancer, considering diverse aspects such as traditional culture, ACP education and training, legislative support, and healthcare system refinement.

Academic-practice partnerships in evidence-based nursing practice: A theory-guided scoping review.

BACKGROUND: Academic-practice partnerships have the potential to solve many challenges in evidence-based nursing practice which is crucial for high-quality care. AIMS: To identify the existing knowledge on academic-practice partnerships in evidence-based nursing practice. METHODS: We conducted this review following the Joanna Briggs Institute scoping review methodology. We performed a comprehensive literature search of nine databases as well as five websites for gray literature. Two researchers independently conducted literature screening and data extraction and analysis. A third researcher was involved when needed. RESULTS: Dedicated time, dedicated resources, and compatible goals were found to be the top three inputs in academic-practice partnerships for evidence-based nursing practice. Meeting and discussion were the most popular forms of activities. Sufficient resources were the most important facilitators. Insufficient resources, insufficient time, and communication issues were the top three barriers. CONCLUSIONS: The assumption proposed in the practice-academic partnership logic model (i.e., inputs plus activities can lead to outputs and outcomes) was preliminarily verified by the results of this review in the context of evidence-based nursing practice. Academic-practice partnerships can leverage the advantages of both sides to overcome barriers and promote evidence-based nursing practice. However, it is essential to conduct a broader range of high-quality studies. Such endeavors could offer more comprehensive evidence for refining the framework of academic-practice partnerships in evidence-based nursing practice. IMPLICATIONS FOR NURSING EDUCATION, PRACTICE, POLICY AND RESEARCH: The "theoretical framework of academic-practice partnerships in evidence-based nursing practice" could theoretically guide academic and clinical nursing staff to collaborate on evidence-based nursing practice and related research and education programs. The academic-practice partnerships in evidence-based nursing practice could lead to a win-win situation for both the academic and the clinical sides. Furthermore, the results of this study provide an evidence-based foundation for policymakers to develop supportive policies for academic-practice partnerships in evidence-based nursing practice.

NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin.

BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

Barriers and facilitators to patient education provided by nurses: A mixed-method systematic review.

AIM: To investigate the factors that facilitate or hinder nurses in providing patient education. DESIGN: A mixed-method systematic review. DATA SOURCES: Six databases (Cochrane Library, PubMed, EMBASE, Web of Science, MEDLINE and ERIC) were systematically searched for relevant publications. METHODS: The study was conducted following the JBI for mixed-method systematic reviews, and the reporting followed the PRISMA guideline. Two researchers independently performed literature screening, literature evaluation, data extraction and synthesis. PROSPERO registration number: CRD42023427451. RESULTS: Twenty-six eligible articles were included, including 15 quantitative articles, 10 qualitative articles and 2 mixed-methods articles. The resultant synthesis of key findings led to the identification of these barriers and facilitators, categorised into five distinct levels: nurse-related factors, organisational factors, patient-related factors, the nurse-patient relationship and interdisciplinary collaboration. CONCLUSIONS: The findings highlight the factors that facilitate or hinder nurses in providing patient education, suggesting that multifaceted interventions can enhance the practice of patient education in nursing and support the development of appropriate patient education guidelines or public policies. RELEVANCE TO CLINICAL PRACTICE: This review delineates the facilitators and barriers influencing nurses' provision of patient education, offering an initial framework for nursing managers to craft interventions aimed at enhancing the quality of patient education provided by nurses, consequently elevating the overall quality of nursing.

Effectiveness of psychological interventions among community-dwelling older adults with subthreshold depression: A systematic review and meta-analysis.

BACKGROUND: Little is known about the effectiveness of psychological interventions among older adults with subthreshold depression in the community. This systematic review and meta-analysis aimed to examine the effectiveness of psychological interventions on depressive symptoms, anxiety symptoms and quality of life. METHODS: We searched five databases from inception to 20th September 2022 and included RCTs that evaluated the effectiveness of psychological interventions among older adults with subthreshold depression in the community. Standardized mean difference (SMD) and 95 % confidence intervals (CI) were used to calculate the effect sizes of treatment outcomes in the meta-analysis, using RevMan 5.4.1 and Stata 16.0. RESULTS: This meta-analysis included thirteen RCT studies involving 2079 participants. Psychological interventions could significantly reduce depressive symptoms (post-intervention time: SMD = -0.58, 95 % CI = -0.76 to -0.40; follow-up time: SMD = -0.31, 95 % CI = -0.41 to -0.22) and anxiety symptoms (post-intervention time: SMD = -0.33, 95 % CI = -0.49 to -0.17; follow-up time: SMD = -0.24, 95 % CI = -0.36 to -0.12) and improve quality of life (post-intervention time: SMD = 0.30, 95 % CI = 0.05 to 0.55; follow-up time: SMD = 0.15, 95 % CI = 0.01 to 0.28). CONCLUSION: Evidence suggests that psychological interventions could significantly reduce depressive symptoms and anxiety symptoms, and improve quality of life among community-dwelling older adults with subthreshold depression.

The impact of frailty on short-term prognosis in discharged adult stroke patients: A multicenter prospective cohort study.

BACKGROUND: Frailty is commonly observed in stroke patients and it is associated with adverse outcomes. However, there remains a gap in longitudinal studies investigating the causal relationship between baseline frailty and short-term prognosis in discharged adult stroke patients. OBJECTIVE: To examine the causal impact of frailty on non-elective readmission and major adverse cardiac and cerebral events, and investigate its associations with cognitive impairment and post-stroke disability. DESIGN: A multicenter prospective cohort study. SETTING: Two tertiary hospitals in Central and Northwest China. PARTICIPANTS: 667 adult stroke patients in stroke units were included from January 2022 to June 2022. METHODS: Baseline frailty was assessed by the Frailty Scale. Custom-designed questions were utilized to assess non-elective readmission and major adverse cardiac and cerebral events as primary outcomes. Cognitive impairment, assessed using the Mini-Mental State Examination Scale (MMSE), and post-stroke disability, measured with the Modified Rankin Scale (mRS), were considered secondary outcomes at a 3-month follow-up. The impact of baseline frailty on non-elective readmission and major adverse cardiac and cerebral events was examined using bivariate and multiple Cox regression analyses. Furthermore, associations between baseline frailty and cognitive impairment, or post-stroke disability, were investigated through generalized linear models. RESULTS: A total of 5 participants died, 12 had major adverse cardiac and cerebral events, and 57 had non-selective readmission among 667 adult stroke patients. Frailty was an independent risk factor for non-selective readmission (hazard ratio [HR]: 2.71, 95 % confidence interval [CI]: 1.59, 4.62) and major adverse cardiac and cerebral events (HR: 3.77, 95 % CI: 1.07, 13.22) for stroke patients. Baseline frailty was correlated with cognitive impairment (regression coefficient [ß]: -2.68, 95 % CI: -3.78, -1.58) adjusting for socio-demographic and clinical factors and follow-up interval. However, the relationship between frailty and cognitive impairment did not reach statistical significance when further adjusting for baseline MMSE (ß: -0.39, 95 % CI: -1.43, 0.64). Moreover, baseline frailty was associated with post-stroke disability (ß: 0.36, 95 % CI: 0.08, 0.65) adjusting for socio-demographic and clinical variables, follow-up interval, and baseline mRS. CONCLUSIONS: The finding highlights the importance of assessing baseline frailty in discharged adult stroke patients, as it is significantly associated with non-elective readmission, major adverse cardiac and cerebral events, and post-stroke disability at 3 months. These results highlight the crucial role of screening and evaluating frailty status in improving short-term prognosis for adult stroke patients. Interventions should be developed to address baseline frailty and mitigate the short-term prognosis of stroke. TWEETABLE ABSTRACT: Baseline frailty predicts non-elective readmission, major adverse cardiac and cerebral events, and post-stroke disability in adult stroke patients. @haiyanhexyyy.

Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1.

Aging increases the risks of various diseases and the vulnerability to death. Cellular senescence is a hallmark of aging that contributes greatly to aging and aging-related diseases. This study demonstrates that extracellular vesicles from human urine-derived stem cells (USC-EVs) efficiently inhibit cellular senescence in vitro and in vivo. The intravenous injection of USC-EVs improves cognitive function, increases physical fitness and bone quality, and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging mice. The anti-aging effects of USC-EVs are not obviously affected by the USC donors' ages, genders, or health status. Proteomic analysis reveals that USC-EVs are enriched with plasminogen activator urokinase (PLAU) and tissue inhibitor of metalloproteinases 1 (TIMP1). These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases, cyclin-dependent kinase inhibitor 2A (P16INK4a), and cyclin-dependent kinase inhibitor 1A (P21cip1). These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins.

The Effectiveness of Cognitive Behavioral Therapy-Based Intervention on Improving Sleep-Related Outcomes for People with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Sleep-related outcomes in people with diabetes are poor, which is closely linked to reducing the development of diabetes. Cognitive behavioral therapy (CBT) based intervention presents innovative solutions that can help improve sleep-related outcomes. Aim: This synthesis aims to assess the effectiveness of CBT-based intervention compared to controls in Randomized Controlled Trials (RCTs) for sleep-related outcomes among people with diabetes. Methods: Eight electronic databases were systematically searched: PubMed, EMBASE, Cochrane library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), and Wan Fang database. We examined CBT-based intervention's effectiveness on sleep-related outcomes in people with diabetes in RCTs identified in these databases from their inception to 1st November 2023, and updated on 15 January 2024. The risk of bias was assessed using the Cochrane Risk of Bias tool by two reviewers. The meta-analysis of included studies was conducted by RevMan 5.3 software. Results: Seven studies in total (n = 2633 participants) were included in this systematic review based on our inclusion criteria. The systematic review found CBT-based intervention significantly improved sleep quality (Pittsburgh Sleep Quality Index, PSQI scores) at immediate post-intervention [95% CI=(-1.31 to -0.32), p = 0.001], six months [95% CI=(-0.75 to -0.22), p = 0.0003], and 12 months [95% CI=(-0.72 to -0.24), <0.0001], compared to control groups. Furthermore, our findings demonstrated that six sessions [95% CI= (-0.38 to -0.13), p < 0.0001] or more than six sessions [95% CI=(-1.76 to -0.02), p = 0.05] of CBT-based intervention could improve sleep quality compared to controls (I2=0%). Interestingly, CBT-based intervention improves total sleep time at post-intervention in people with diabetes compared to the control group [95% CI= (-0.57 to -0.12), p = 0.003]. However, there was no significant that CBT-based intervention is beneficial to time to fall asleep [95% CI (-1.89 to 0.43), p = 0.22] and sleep efficiency [95% CI (-1.27 to 0.27), p = 0.20] after intervention, compared to control group. Conclusion: CBT-based intervention appears to have a beneficial effect on improving sleep quality and total sleep time among people with diabetes. CBT-based intervention could be considered a strategy among healthcare providers to enhance sleep quality and total sleep time for people with diabetes. More RCTs with rigorous designs and long-term follow-up are warranted to provide conclusive evidence of the CBT-based intervention on sleep-related outcomes and to explore the mechanisms by which the CBT-based interventions improve sleep-related outcomes.

Ethanol extract of Cyathulae Radix inhibits osteoclast differentiation and bone loss.

Cyathulae Radix, a traditional Chinese medicine and a common vegetable, boasts a history spanning millennia. It enhances bone density, boosts metabolism, and effectively alleviates osteoporosis-induced pain. Despite its historical use, the molecular mechanisms behind Cyathulae Radix's impact on osteoporosis remain unexplored. In this study, we investigated the effects and mechanisms of Cyathulae Radix ethanol extract (CEE) in inhibiting osteoporosis and osteoclastogenesis. Eight-week-old female mice underwent ovariectomy and were treated with CEE for eight weeks. Micro-computed tomography (micro-CT) assessed histomorphometric parameters, bone tissue staining observed distal femur histomorphology, and three-point bending tests evaluated tibia mechanical properties. Enzyme-linked immunosorbent assay (ELISA) measured serum estradiol (E2), receptor activator for nuclear factor B ligand (RANKL), and osteoprotegerin (OPG) levels. Osteoclastogenesis-related markers were analyzed via Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase (TRAP) staining, qRT-PCR, and WB assay. Compared with the ovariectomy (OVX) group, CEE treatment enhanced trabecular bone density, maximal load-bearing capacity, and various histomorphometric parameters. Serum E2 and OPG levels significantly increased, while Receptor activator of nuclear factor-κB (RANK) decreased in the CEE group. CEE downregulated matrix metallopeptidase 9 (MMP-9), Cathepsin K (CTSK), and TRAP gene and protein expression. In bone marrow macrophages (BMMs), CEE reduced mature osteoclasts, bone resorption pit areas, and MMP-9, CTSK, and TRAP expression during osteoclast differentiation. Compared with DMSO treatment, CEE markedly inhibited RANK, TNF receptor associated factor 6 (TRAF6), Proto-oncogene c-Fos (c-Fos), Nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expressions, and Extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), NF-kappa B-p65 (p65) phosphorylation in osteoclasts. In conclusion, CEE significantly inhibits OVX-induced osteoporosis and RANKL-induced osteoclastogenesis, potentially through modulating the Estrogen Receptor (ER)/RANK/NFATc1 signaling pathway.

An inoculation site-retained mRNA vaccine induces robust immune responses against SARS-CoV-2 variants.

mRNA-based vaccines and therapeutic agents hold great promise in prevention and treatment of human diseases, yet high percentage of systemic adverse effect in clinic remains a big safety concern. One major potential cause is a high level of leakage of the locally inoculated mRNA vaccine nanoparticles into circulation. We have screened and optimized a core-shell structured lipopolyplex (LPP) formulation for mRNA with a tissue-retention property. Upon intramuscular inoculation, the mRNA-encapsulated LPP nanoparticles were preferentially taken up by the phagocytic antigen-presentation cells, and potently promoted dendritic cell maturation. We applied the new formulation to prepare a prophylactic vaccine for SARS-CoV-2, and observed potent humoral and cellular immune responses from the vaccine in both murine models and non-human primates. More importantly, the vaccine demonstrated a benign safety profile in non-human primates, with limited side effects after repeated treatment with high dosages of LPP/mRNA. Taken together, the inoculation site-retained vaccine formulation serves as a promising vehicle for mRNA vaccines and therapeutic agents.

Sulfasalazine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress and nuclear factor-kappaB pathways.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not fully understood. The lipopolysaccharide (LPS)-induced mouse model of ALI has been widely used to study human ALI/ARDS. Sulfasalazine (SASP) has antibacterial and anti-inflammatory effects and is used for treating inflammatory bowel and rheumatic diseases. However, the effect of SASP on LPS-induced ALI in mice has not yet been reported. Therefore, we aimed to investigate the effect of SASP on LPS-induced ALI in mice. Mice were intraperitoneally injected with SASP 2 h before or 4 h after LPS modeling. Pulmonary pathological damage was measured based on inflammatory factor expression (malondialdehyde and superoxide dismutase levels) in the lung tissue homogenate and alveolar lavage fluid. The production of inflammatory cytokines and occurrence of oxidative stress in the lungs induced by LPS were significantly mitigated after the prophylactic and long-term therapeutic administration of SASP, which ameliorated ALI caused by LPS. SASP reduced both the production of inflammatory cytokines and occurrence of oxidative stress in RAW264.7 cells, which respond to LPS. Moreover, its mechanism contributed to the suppression of NF-κB and nuclear translocation. In summary, SASP treatment ameliorates LPS-induced ALI by mediating anti-inflammatory and antioxidant effects, which may be attributed to the inhibition of NF-κB activation and promotion of antioxidant defenses. Thus, SASP may be a promising pharmacologic agent for ALI therapy.

Association of Valproic Acid and Its Main Metabolites' Plasma Concentrations with Clinical Outcomes among Epilepsy Patients: A 10-Year Retrospective Study Based on Therapeutic Drug Monitoring.

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 µg/mL) is inadequate for predicting clinical outcomes. Additionally, the relationship between VPA metabolites and clinical outcomes remains unclear. In this retrospective study, 485 Chinese Southern Han epilepsy patients receiving VPA monotherapy were analyzed after reaching steady-state levels. Plasma concentrations of VPA and its five main metabolites were determined by liquid chromatography-mass spectrometry (LC-MS). We assessed the relevance of the recommended therapeutic VPA range for clinical outcomes and explored the association between VPA/metabolites levels and treatment efficacy/adverse effects. Vitro experiments were conducted to assess 4-ene-VPA hepatotoxicity. The therapeutic range of VPA exhibited no significant correlation with clinical outcomes, and plasma concentrations of VPA failed to serve as predictive indicators for treatment response/adverse effects. Treatment responders had higher 2-PGA concentrations (median, 26.39 ng/mL versus 13.68 ng/mL), with a threshold of 36.5 ng/mL for optimal epilepsy treatment. Patients with abnormal liver function had a higher 4-ene-VPA median concentration (6.41 µg/mL versus 4.83 µg/mL), and the ratio of 4-ene-VPA to VPA better predicted VPA-induced hepatotoxicity (area under the curve, 0.718) than 4-ene-VPA concentration. Vitro experiments revealed that 4-ene-VPA was more hepatotoxic than VPA in HepaRG and L02 cell lines. Total plasma VPA concentration does not serve as a predictor of clinical outcomes. 2-PGA concentrations may be associated with efficacy, whereas the ratio of 4-ene-VPA to VPA may be considered a better biomarker (threshold 10.03%) for VPA-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This was the first and largest observational cohort in China to explore the relationship between patients' parent and metabolites concentrations of VPA and clinical outcomes during the maintenance of VPA monotherapy in epileptic patients. This study provided feasible references of VPA for epilepsy clinical treatment with a larger sample of patients compared with previous studies for a more definitive conclusion based on real-world situations. We found two potential biomarkers in predicting efficacy and liver injury, respectively. This breakthrough has the potential to assist in the rational use of VPA.

Stages of readiness for advance care planning: Systematic review and meta-analysis of prevalence rates and associated factors.

BACKGROUND: Advance care planning has been widely recommended to respect the medical care preferences of patients in the final stages of life. However, uptake of advance care planning in healthcare settings remains suboptimal. It may be beneficial to take into account individuals' readiness for advance care planning based on the stages to change identified in the Transtheoretical Model. OBJECTIVE: To identify the measurements used to assess readiness of advance care planning based on the Transtheoretical Model, to pool the prevalence of readiness stages, and to summarize the factors affecting people's readiness for advance care planning. DESIGN: Systematic review and meta-analysis. METHODS: We systematically searched the databases of PubMed, EMBASE, The Cochrane Library, CINAHL, and Web of Science for relevant studies from inception to February 2023. A random effects model was used to estimate the pooled prevalence. And a narrative review on the factors associated with stages of readiness was conducted. RESULTS: This meta-analysis included 25 studies involving a total of 4237 individuals. The precontemplation stage was the most commonly identified stage of readiness among advance care planning behaviors (26-72 %). The prevalence of readiness stages for advance care planning varied among different types of behavior. The behavior of "talking to health care proxy/family/loved ones about thoughts on quality versus quantity of life" had the highest level of readiness among all listed behaviors, followed by "talking to health care proxy/family/loved ones about living will", "signing a health care proxy form" and "signing a living will", "signing an advance directive", as well as "talking to doctors about living will". Regarding to influencing factors, a majority of sociodemographic and clinical factors did not show consistent associations with readiness, but some studies did suggest potential links with age, health status, countries, type of assessment, core structures of the Transtheoretical Model, and intervention modalities. CONCLUSIONS: A majority of individuals were unaware of advance care planning. There is an urgent need to promote readiness for such planning. Starting with preliminary activities such as "talking to health care proxy/family/loved ones about thoughts on quality versus quantity of life" can help initiate advance care planning. Better integration of the Transtheoretical Model and interventions into the research of advance care planning readiness are needed. REGISTRATION: Not registered.

Evaluation of dynamic control of continuous capture with periodic counter-current chromatography under feedstock variations.

Multi-column periodic counter-current chromatography is a promising technology for continuous antibody capture. However, dynamic changes due to disturbances and drifts pose some potential risks for continuous processes during long-term operation. In this study, a model-based approach was used to describe the changes in breakthrough curves with feedstock variations in target proteins and impurities. The performances of continuous capture of three-column periodic counter-current chromatography under ΔUV dynamic control were systematically evaluated with modeling to assess the risks under different feedstock variations. As the concentration of target protein decreased rapidly, the protein might not breakthrough from the first column, resulting in the failure of ΔUV control. Small reductions in the concentrations of target proteins or impurities would cause protein losses, which could be predicted by the modeling. The combination of target protein and impurity variations showed complicated effects on the process performance of continuous capture. A contour map was proposed to describe the comprehensive impacts under different situations, and nonoperation areas could be identified due to control failure or protein loss. With the model-based approach, after the model parameters are estimated from the breakthrough curves, it can rapidly predict the process stability under dynamic control and assess the risks under feedstock variations or UV signal drifts. In conclusion, the model-based approach is a powerful tool for continuous process evaluation under dynamic changes and would be useful for establishing a new real-time dynamic control strategy.

Perceptions of primary health care nurses and general practitioners in the care of older people with urinary incontinence.

AIMS: To identify the challenges and opportunities among primary health care nurses and general practitioners (GPs) in the care of older people with urinary incontinence (UI) and other chronic conditions in China. BACKGROUND: UI is highly prevalent among community-dwelling older people with chronic conditions but is underreported and poorly managed. Understanding the factors that affect primary health care professionals' practices in their care for this population is imperative to foster nurse-led UI care services. DESIGN: A qualitative descriptive study. METHODS: Four focus groups were held with 24 primary health care nurses and GPs in Changsha, Hunan Province, China, between July and September 2021. A reflective thematic analysis was used to identify themes. RESULTS: This study revealed misconceptions regarding older people living with UI and other chronic conditions in primary care health professional participants. Moreover, primary health care nurses had very limited autonomy in UI diagnosis and initiating care interventions for this patient population. By reflecting on practices, participants recognized various practical solutions to improve the detection and management of UI. Participants also identified barriers to accessing care services in older people with UI. They suggested changes in the health care system to achieve universal access to UI care services for older people. CONCLUSION: Nurse-led UI care services in primary health care for community-dwelling older people with chronic conditions are in high demand but are underdeveloped due to professional and health care system factors. IMPACT: Findings from this study provide new insights into challenges faced by primary health care professionals and illuminate practical solutions to address these challenges. REPORTING METHODS: Adherence to COREQ guidelines was maintained. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Demographics moderated the association of symptom burden with falls and fall-related outcomes.

OBJECTIVES: To examine whether (1) prior-year symptom burden predicted later-year falls and fall-related outcomes and (2) demographics moderated the longitudinal effects of symptom burden on falls and fall-related outcomes among community-dwelling older adults. METHODS: We used 2011-2018 National Health and Aging Trends Study data that included 9,060 community-dwelling older adults (contributed 34,327 observations). Falls and fall-related outcomes included self-reported falls, multiple falls, fear of falling (FOF), and FOF limiting activity. Symptom burden was defined as the presence of pain, insomnia, breathing difficulty, depressive symptoms, anxiety, and fatigue, and calculated the number of symptoms (range from 0 to 6). Binomial logistic regression was used to examine the associations between symptom burden and falls and fall-related outcomes and the moderation effects of demographic factors. RESULTS: The majority of the sample were aged between 65 and 79 years old (57.7%), non-Hispanic White (70.5%), and female (58.4%). Each additional symptom was associated with an increased risk of falls (Adjusted Odds Ratio [AOR]: 1.13, 95% CI: 1.10-1.15), multiple falls (AOR: 1.15, 95% CI: 1.12-1.18), FOF (AOR: 1.20, 95% CI: 1.18-1.23), and FOF limiting activity (AOR: 1.24, 95% CI: 1.20-1.28). Age, race/ethnicity, education, and living arrangement statistically significantly moderated the relationships between symptom burden and falls and fall-related outcomes. CONCLUSIONS: Symptom burden predicted falls, multiple falls, FOF and FOF limiting activity, and demographics may differentially modify this risk. Individually tailored symptom assessment and management plans should be incorporated into fall risk assessment and interventions for community-dwelling older adults living.

Screening instruments for early identification of unmet palliative care needs: a systematic review and meta-analysis.

BACKGROUND: The early detection of individuals who require palliative care is essential for the timely initiation of palliative care services. This systematic review and meta-analysis aimed to (1) Identify the screening instruments used by health professionals to promote early identification of patients who may benefit from palliative care; and (2) Assess the psychometric properties and clinical performance of the instruments. METHODS: A comprehensive literature search was conducted in PubMed, Embase, CINAHL, Scopus, CNKI and Wanfang from inception to May 2023. We used the COnsensus-based Standards for the Selection of Health Measurement INstruments to assess the methodological quality of the development process for the instruments. The clinical performance of the instruments was assessed by narrative summary or meta-analysis. Subgroup analyses were conducted where necessary. The quality of included studies was assessed using the Newcastle-Ottawa Scale and the Cochrane Collaboration's risk of bias assessment tool. RESULTS: We included 31 studies that involved seven instruments. Thirteen studies reported the development and validation process of these instruments and 18 studies related to assessment of clinical performance of these instruments. The content validity of the instruments was doubtful or inadequate because of very low to moderate quality evidence. The pooled sensitivity (Se) ranged from 60.0% to 73.8%, with high heterogeneity (I2 of 88.15% to 99.36%). The pooled specificity (Sp) ranges from 70.4% to 90.2%, with high heterogeneity (I2 of 96.81% to 99.94%). The Supportive and Palliative Care Indicators Tool (SPICT) had better performance in hospitals than in general practice settings (Se=79.8% vs 45.3%, p=0.004; Sp=59.1% vs 97.0%, p=0.000). CONCLUSION: The clinical performance of existing instruments in identifying patients with palliative care needs early ranged from poor to reasonable. The SPICT is used most commonly, has better clinical performance than other instruments but performs better in hospital settings than in general practice settings.

Instruments for measuring nursing research competence: a COSMIN-based scoping review.

AIM: The aim of this scoping review was to evaluate and summarise the measurement properties of nursing research competence instruments and provide a summary overview of the use of nursing research competence instruments. BACKGROUND: Increasing nursing research competence instruments have been developed. However, a systematic review and evaluation of nursing research competence instruments is lacking. METHOD: This scoping review was conducted following the Joanna Briggs Institute updated methodology for scoping reviews and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Reviewers searched articles in Eight English databases and two Chinese databases between April 1st, 2022, and April 30th, 2022. An updated literature search was conducted between March 1st and March 4th, 2023. The literature screening and data extraction were conducted by two reviewers, independently. A third reviewer was involved when consensus was needed. The COnsensus-based Standards for the selection of health Measurement Instruments methodology was used to evaluate the methodological quality and measurement properties of the nursing research competence instruments. RESULTS: Ten studies involving eight nursing research competence instruments were included. None of the existing instruments have assessed all measurement properties. A total of 177 empirical studies have utilized a nursing research competence instrument with tested measurement properties. CONCLUSION: 'Self-evaluated Nursing Research Capacity of Questionnaire (refined)' was identified as the most appropriate nursing research competence instrument in existing instruments. However, reviewers need to conduct further measurement properties studies on the existing nursing research competence instruments. IMPLICATIONS FOR THE NURSING POLICY: This study could guide the selection of appropriate nursing research competence instruments which could help to evaluate the nursing research competence of nurses and inform the development of intervention plans to enhance nursing research competence.

Sirtuin1 Mediates the Protective Effects of Echinacoside against Sepsis-Induced Acute Lung Injury via Regulating the NOX4-Nrf2 Axis.

Currently, the treatment for sepsis-induced acute lung injury mainly involves mechanical ventilation with limited use of drugs, highlighting the urgent need for new therapeutic options. As a pivotal aspect of acute lung injury, the pathologic activation and apoptosis of endothelial cells related to oxidative stress play a crucial role in disease progression, with NOX4 and Nrf2 being important targets in regulating ROS production and clearance. Echinacoside, extracted from the traditional Chinese herbal plant Cistanche deserticola, possesses diverse biological activities. However, its role in sepsis-induced acute lung injury remains unexplored. Moreover, although some studies have demonstrated the regulation of NOX4 expression by SIRT1, the specific mechanisms are yet to be elucidated. Therefore, this study aimed to investigate the effects of echinacoside on sepsis-induced acute lung injury and oxidative stress in mice and to explore the intricate regulatory mechanism of SIRT1 on NOX4. We found that echinacoside inhibited sepsis-induced acute lung injury and oxidative stress while preserving endothelial function. In vitro experiments demonstrated that echinacoside activated SIRT1 and promoted its expression. The activated SIRT1 was competitively bound to p22 phox, inhibiting the activation of NOX4 and facilitating the ubiquitination and degradation of NOX4. Additionally, SIRT1 deacetylated Nrf2, promoting the downstream expression of antioxidant enzymes, thus enhancing the NOX4-Nrf2 axis and mitigating oxidative stress-induced endothelial cell pathologic activation and mitochondrial pathway apoptosis. The SIRT1-mediated anti-inflammatory and antioxidant effects of echinacoside were validated in vivo. Consequently, the SIRT1-regulated NOX4-Nrf2 axis may represent a crucial target for echinacoside in the treatment of sepsis-induced acute lung injury.