Development of a Humanized Antibody Targeting Extracellular HSP90α to Suppress Endothelial-Mesenchymal Transition-Enhanced Tumor Growth of Pancreatic Adenocarcinoma Cells.

Extracellular HSP90α (eHSP90α) is a promoter of tumor development and malignant progression. Patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC), have generally shown 5~10-fold increases in serum/plasma eHSP90α levels. In this study, we developed a humanized antibody HH01 to target eHSP90α and evaluated its anticancer efficacy. HH01, with novel complementarity-determining regions, exhibits high binding affinity toward HSP90α. It recognizes HSP90α epitope sites 235AEEKEDKEEE244 and 251ESEDKPEIED260, with critical amino acid residues E237, E239, D240, K241, E253, and K255. HH01 effectively suppressed eHSP90α-induced invasive and spheroid-forming activities of colorectal cancer and PDAC cell lines by blocking eHSP90α's ligation with the cell-surface receptor CD91. In mouse models, HH01 potently inhibited the tumor growth of PDAC cell grafts/xenografts promoted by endothelial-mesenchymal transition-derived cancer-associated fibroblasts while also reducing serum eHSP90α levels, reflecting its anticancer efficacy. HH01 also modulated tumor immunity by reducing M2 macrophages and reinvigorating immune T-cells. Additionally, HH01 showed low aggregation propensity, high water solubility, and a half-life time of >18 days in mouse blood. It was not cytotoxic to retinal pigmented epithelial cells and showed no obvious toxicity in mouse organs. Our data suggest that targeting eHSP90α with HH01 antibody can be a promising novel strategy for PDAC therapy.

Enhancing Cordycepin in Functional Porridge through Rice Varietal Fermentation with Cordyceps militaris (Ascomycetes) and Utilizing Non-Targeted Metabolomics for Process Enhancement.

Cordyceps militaris, a medicinal fungus rich in cordycepin, shows promise in treating diseases such as cancer, respiratory issues, and COVID-19. This study examines the impact of different Taiwanese rice varieties on its solid-state fermentation, focusing on optimizing cordycepin production. The results indicated that the cordycepin yield was indeed affected by the type of rice used. In terms of the fruiting bodies, germ rice resulted in the highest yield (13.1 ± 0.36 mg/g), followed by brown rice (11.9 ± 0.26 mg/g). In the rice culture medium (RCM), brown rice led to the highest yield (4.77 ± 0.06 mg/g). Using gas chromatography-mass spectrometry and untargeted metabolomics, the study identifies four key volatile components linked to cordycepin, providing insights into developing functional rice porridge products. These findings are significant for advancing cordycepin mass production and offering dietary options for older individuals.

Active DNA Demethylase, TET1, Increases Oxidative Phosphorylation and Sensitizes Ovarian Cancer Stem Cells to Mitochondrial Complex I Inhibitor.

Ten-eleven translocation 1 (TET1) is a methylcytosine dioxygenase involved in active DNA demethylation. In our previous study, we demonstrated that TET1 reprogrammed the ovarian cancer epigenome, increased stem properties, and activated various regulatory networks, including metabolic networks. However, the role of TET1 in cancer metabolism remains poorly understood. Herein, we uncovered a demethylated metabolic gene network, especially oxidative phosphorylation (OXPHOS). Contrary to the concept of the Warburg effect in cancer cells, TET1 increased energy production mainly using OXPHOS rather than using glycolysis. Notably, TET1 increased the mitochondrial mass and DNA copy number. TET1 also activated mitochondrial biogenesis genes and adenosine triphosphate production. However, the reactive oxygen species levels were surprisingly decreased. In addition, TET1 increased the basal and maximal respiratory capacities. In an analysis of tricarboxylic acid cycle metabolites, TET1 increased the levels of α-ketoglutarate, which is a coenzyme of TET1 dioxygenase and may provide a positive feedback loop to modify the epigenomic landscape. TET1 also increased the mitochondrial complex I activity. Moreover, the mitochondrial complex I inhibitor, which had synergistic effects with the casein kinase 2 inhibitor, affected ovarian cancer growth. Altogether, TET1-reprogrammed ovarian cancer stem cells shifted the energy source to OXPHOS, which suggested that metabolic intervention might be a novel strategy for ovarian cancer treatment.

Association of intrinsic capacity and medication non-adherence among older adults with non-communicable diseases in Taiwan.

OBJECTIVES: Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study aimed to examine the association of medication non-adherence with level of overall intrinsic capacity (IC), pattern of IC, and specific IC component among older adults with NCDs. METHODS: A cross-sectional questionnaire-based survey of 1268 older adults aged 60 years and above was conducted in 2022 in southern Taiwan. Among them, 894 suffered from 1 more NCD were included in this study. The Integrated Care for Older People Screening Tool for Taiwanese and the Adherence to Refills and Medication Scale were used to assess IC and medication non-adherence, respectively. Latent class analysis (LCA) was used to identify patterns of IC impairment, and binary logistic regression was used to assess the association between medication non-adherence and IC. RESULTS: Older adults in the moderate (score: 1-2) or low (score≧3) overall IC groups were more likely to experience medication non-adherence (moderate: adjusted odds ratio (aOR) 1.57 [95% CI: 1.05-2.36]; low: 2.26 [1.40-3.67]). The "physical and nutritional impairments accompanied by depressive symptoms" group was associated with statistically higher odds of medication non-adherence (aOR 1.66 [1.01-2.73]). Older adults with cognitive impairment, hearing loss, or depressive symptoms showed greater likelihood of medication non-adherence (cognitive impairment: aOR 1.53 [1.03-2.27]; hearing loss: aOR 1.57 [1.03-2.37]; depressive symptoms: aOR 1.81 [1.17-2.80]). CONCLUSIONS: Intervention for improving medication non-adherence among older adults with NCDs should consider IC.

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

Anti-Hyperuricemia Activity and Potential Mechanisms of Medicinal Mushroom Activity: A Review of Preclinical Studies.

Hyperuricemia (HUA) is characterized by abnormally elevated levels of serum uric acid, the product of purine metabolism. The primary symptom of HUA is gout; however, asymptomatic HUA is associated with complications such as hypertension, kidney disease, cardiovascular disease, and metabolic syndrome. The activation of xanthine oxidase (XO), a pivotal enzyme in uric acid biosynthesis, is coupled with extensive reactive oxygen species generation, leading to inflammatory responses, and triggers the development of HUA and its complications. In clinical practice, XO inhibitors are primarily used to treat HUA; however, their prolonged use is accompanied by serious adverse effects. Mushrooms and their bioactive constituents have shown promising anti-HUA activities in both in vitro and in vivo studies, including inhibition of urate production, modulation of renal urate transporters, enhancement of intestinal uric acid excretion, and antioxidant, anti-inflammatory, and antimetabolic syndrome properties. Clinical trials are necessary to validate the beneficial effects and safety of mushrooms in preventing or alleviating HUA and attenuating the associated complications. This review presents contemporary insights into the pathogenesis of HUA, the bioactive components of mushrooms, their therapeutic potential, and the underlying mechanisms involved in ameliorating HUA.

Dual-task training in older adults with cognitive impairment: A meta-analysis and trial sequential analysis of randomized controlled trials.

OBJECTIVE: To determine the effects of simultaneous dual-task training on cognitive function, physical function, and depression in older adults with mild cognitive impairment or dementia. METHODS: Comprehensive database searches were conducted in PubMed, Embase, the Cochrane Library, CINAHL, Ovid-Medline, Web of Science, and Scopus up to December 2022. Randomized controlled trials were included to assess the efficacy of simultaneous dual-task training for older adults with mild cognitive impairment or dementia. The analysis utilized Comprehensive Meta-Analysis version 3.0, presenting Hedges' g and the corresponding 95 % confidence interval (CI) for the pooled effect size and, applying a random-effects model. The I2 and Cochran's Q tests were employed to evaluate heterogeneity. The Cochrane Risk of Bias 2.0 tool was employed to assess study quality. The Copenhagen Trial Unit (version 0.9.5.10 Beta) was employed for trial sequential analysis, providing a rigorous methodology for evaluating cumulative evidence from multiple studies. RESULTS: Of the 1676 studies identified, 20 studies involving 1477 older adults with cognitive impairment were included. Dual-task training significantly enhanced global cognition (0.477, 95 % CI: 0.282 to 0.671), executive function (-0.310, 95 % CI: -0.586 to -0.035), working memory (0.714, 95 % CI: 0.072 to 1.355), gait (0.418, 95 % CI: 0.252 to 0.583), physical activity (0.586, 95 % CI: 0.012 to 1.16), and depression (-0.703, 95 % CI: -1.253 to -0.153). Trial sequential analyses revealed the robustness of this meta-analysis, which was based on a sufficient sample size from the included studies. Moreover, dual-task training demonstrated beneficial effects on global cognition, executive function, working memory, and gait. CONCLUSIONS: Dual-task training improved cognition, physical function, and depression among older adults with cognitive impairment. Accordingly, dual-task training should be considered a clinical nonpharmacological intervention for older adults with mild cognitive impairment or dementia. Nevertheless, the trial sequential analysis results were consistent with those of the pairwise meta-analysis but only global cognition reached significance by crossing the trial sequential analysis boundary. Future studies with higher-quality designs and larger sample sizes are required to obtain more conclusive results regarding other outcomes. REGISTRATION: PROSPERO CRD42023418598.

Machine learning prediction on wetland succession and the impact of artificial structures from a decade of field data.

The artificial structures can influence wetland topology and sediment properties, thereby shaping plant distribution and composition. Macrobenthos composition was correlated with plant cover. Previous studies on the impact of artificial structures on plant distribution are scarce in incorporating time-series data or extended field surveys. In this study, a machine-learning-based species distribution model with decade-long observation was analyzed to investigate the correlation between the shift in the distribution of B. planiculmis, artificial structure-induced elevation changes and the expansion of other plants, as well as their connection to soil properties and crab composition dynamics under plants in Gaomei Wetland. Long short-term memory model (LSTM) with Shapley additive explanations (SHAP) was employed for predicting the distribution of B. planiculmis and explaining feature importance. The results indicated that wetland topology was influenced by both artificial structures and plants. Areas initially colonized by B. planiculmis were replaced by other species. Soil properties showed significant differences among plant patches; however, principal component analysis (PCA) of sediment properties and niche similarity analysis showed that the niche of plants was overlapped. Crab composition was different under different plants. The presence probability of B. planiculmis near woody paths decreased according to LSTM and field survey data. SHAP analysis suggested that the distribution of other plants, historical distribution of B. planiculmis and sediment properties significantly contributed to the presence probability of B. planiculmis. A sharp decrease in SHAP values with increasing NDVI at suitable elevations, overlap in PCA of sediment properties and niche similarity indicated potential competition among plants. This decade-long time-series field survey revealed the joint effects of artificial structure and vegetation on the topology and soil properties dynamics. These changes influenced the plant distribution through potential plant competition. LSTM with SHAP provided valuable insights in the underlying the mechanisms of artificial structure effects on the plant zonation process.

Changes in cognitive function after a 12-week POWER rehabilitation in older adults with schizophrenia and frailty.

BACKGROUND: The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty. METHODS: Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups. RESULTS: Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint. CONCLUSION: A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning.

Assessing intrinsic capacity in Taiwan: Initial psychometric properties of the Integrated Care for Older People Screening Tool for Taiwanese (ICOPES-TW).

BACKGROUND: The World Health Organization (WHO) proposed the concept of intrinsic capacity (comprising composite physical and mental capacity) which aligns with their concepts of healthy aging and functional ability. Consequently, the WHO promotes the Integrated Care for Older People (ICOPE) framework as guidance for geriatric care. Consequently, each government should have a screening tool corresponding to ICOPE framework to promote geriatric care. The present study examined the initial psychometric properties of the Taiwan version of ICOPE (i.e., ICOPES-TW). METHODS: Older people (n = 1235; mean age = 72.63 years; 634 females [51.3%]) were approached by well-trained interviewers for participation. A number of measures were administered including the ICOPES-TW, WHOQOL-AGE (assessing quality of life [QoL]), Clinical Frailty Scale (assessing frailty), Barthel Index (assessing basic activity of daily living [BADL]), and Lawton Instrumental Activities of Daily Living Scale (assessing instrumental activity of daily living [IADL]). RESULTS: The ICOPES-TW had a two-factor structure (body functionality [eigenvalue = 1.932] and life adaptation [eigenvalue = 1.170]) as indicated by the results of exploratory factor analysis. Internal consistency of the ICOPES-TW was low (Cronbach's α = 0.55 [entire ICOPES-TW], 0.45 (body functionality factor), and 0.52 (life adaptation factor). ICOPES-TW scores were significantly (i) positively correlated with age (r = 0.321), IADL (r = 0.313), and frailty (r = 0.601), and (ii) negatively correlated with QoL (r=-0.447), and BADL (r=-0.447), with all p-values < 0.001. CONCLUSION: The ICOPES-TW could be a useful screening tool for healthcare providers to quickly evaluate intrinsic capacity for Taiwanese older people given that it has moderate to strong associations with age, BADL, IADL, QoL, and frailty.

Algal Oil Mitigates Sodium Taurocholate-Induced Pancreatitis by Alleviating Calcium Overload, Oxidative Stress, and NF-κB Activation in Pancreatic Acinar Cells.

Acute pancreatitis (AP) is characterized by elevated intracellular Ca2+ concentrations, mitochondrial dysfunction, and oxidative stress in pancreatic acinar cells. Algal oil (AO) has demonstrated antioxidant and anti-inflammatory properties. This study aims to explore the effects of algal oil on the microenvironment of AP. Rat pancreatic acinar AR42J cells were pretreated with AO containing 0, 50, 100, or 150 µM of docosahexaenoic acid (DHA) 2 h prior to AP induction using sodium taurocholate (STC). After 1 h of STC treatment, AR42J cells exhibited a significant increase in intracellular Ca2+ concentration and the production of amylase, lipase, reactive oxygen species, and pro-inflammatory mediators, including tumor necrosis factor-α and interleukin-6. These STC-induced increases were markedly reduced in cells pretreated with AO. In comparison to cells without AO, those treated with a high dose of AO before STC exposure demonstrated a significant increase in mitochondrial membrane potential and a decrease in lipid peroxidation. Furthermore, STC-activated nuclear factor kappa-B (NF-κB) was attenuated in AO-pretreated cells, as evidenced by a significant decrease in activated NF-κB. In conclusion, AO may prevent damage to pancreatic acinar cells by alleviating intracellular Ca2+ overload, mitigating mitochondrial dysfunction, reducing oxidative stress, and attenuating NF-κB-targeted inflammation.

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus.

BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). RESULTS: The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. CONCLUSIONS: The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.

Factors associated with loneliness in middle-aged and older patients with breast cancer.

Objective: Loneliness is associated with adverse mental and physical health conditions and increased mortality. In this study, we identified significant factors associated with loneliness in middle-aged and older patients with breast cancer (BC). Methods: For this cross-sectional study, we enrolled 200 patients (aged from 20 to 60 years) with BC from two hospitals in Indonesia through convenience sampling. Demographic characteristics, distress symptoms (Symptom Distress Scale), social support (Multidimensional Scale of Perceived Social Support), frailty (Groningen Frailty Indicator), and loneliness (UCLA Loneliness Scale, version 3) were measured. Multivariate logistic regression was performed to identify significant factors associated with loneliness in our cohort. Results: Loneliness risk was negatively correlated with social support but positively correlated with unemployment and frailty. Thus, the patients received a high level of social support (odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.92-0.99) and had a low risk of severe loneliness. By contrast, patients who were unemployed (OR: 4.00; 95% CI: 1.65-9.66) and those who had frailty (OR: 5.79; 95% CI: 2.50-13.42) had an elevated risk of severe loneliness. Conclusions: Unemployment, social support, and frailty may significantly influence the risk of loneliness in patients with BC. Early and regular assessments of loneliness should be integrated in the care of these patients. Suitable strategies aimed at increasing social support and mitigating frailty may benefit middle-aged and older patients with BC, particularly unemployed patients, by reducing their risk of loneliness.

Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

A body shape index (ABSI) but not body mass index (BMI) is associated with prostate cancer-specific mortality: Evidence from the US NHANES database.

BACKGROUND: Prostate cancer (PCa) is a common malignancy in males and obesity may play a role in its development and progression. Associations between visceral obesity measured by a body shape index (ABSI) and PCa mortality have not been thoroughly investigated. This study assessed the associations between ABSI, body mass index (BMI), and long-term PCa-specific mortality using a nationally representative US database. METHODS: This population-based longitudinal study collected data of males aged ≥40 years diagnosed with PCa and who underwent surgery and/or radiation from the National Health and Nutrition Examination Survey database 2001-2010. All included participants were followed through the end of 2019 using the National Center for Health Statistics Linked Mortality File. Associations between PCa-specific mortality, BMI, and ABSI were determined using Cox proportional hazards regression and receiver operating characteristic (ROC) curve analysis. RESULTS: Data of 294 men (representing 1,393,857 US nationals) were analyzed. After adjusting for confounders, no significant associations were found between BMI (adjusted hazard ratio [aHR] = 1.06, 95% confidence interval [CI]: 0.97-1.16, p = 0.222), continuous ABSI (aHR = 1.29, 95% CI: 0.83-2.02, p = 0.253), or ABSI in category (Q4 vs. Q1-Q3: aHR = 1.52, 95% CI: 0.72-3.24, p = 0.265), and greater risk of PCa-specific mortality. However, among participants who had been diagnosed within 4 years, the highest ABSI quartile but not in BMI was significantly associated with greater risk for PCa-specific mortality (Q4 vs. Q1-Q3: aHR = 5.34, 95% CI: 2.26-12.62, p = 0.001). In ROC analysis for this subgroup, the area under the curve of ABSI alone for predicting PCa-specific mortality was 0.638 (95% CI: 0.448-0.828), reaching 0.729 (95% CI: 0.490-0.968 when combined with other covariates. CONCLUSIONS: In US males with PCa diagnosed within 4 years, high ABSI but not BMI is independently associated with increased PCa-specific mortality.

Efficacy of resilience-related psychological interventions in patients with long-term diseases: A meta-analysis of randomised controlled trials.

Patients with long-term disease experience low resilience, emphasising the importance of psychological interventions to improve resilience. However, there is no comprehensive evidence on the efficacy of resilience-related psychological interventions (RRPIs) in this population. Therefore, we performed a meta-analysis to evaluate and extend knowledge from previous meta-analyses on the efficacy of RRPIs on resilience, stress, anxiety, depression and quality of life among patients with long-term disease. Cochrane Library, Embase, Ovid-MEDLINE, PubMed, Scopus, Web of Science and CINAHL electronic databases were searched until 3 February 2023. The pooled effect size of the efficacy of RRPIs was calculated using the Hedges' g (g) with random-effects model, while Cochrane Q-statistics and I2 tests assessed heterogeneity in Comprehensive Meta-Analysis 3.0 software. The Cochrane Risk of Bias 2.0 tool evaluated the quality of studies. Moderator analysis was used to explore sources of heterogeneity. Twenty randomised controlled trial studies were identified, representing a total of 1388 individuals with long-term disease. RRPIs significantly enhance resilience (g = 0.79), alleviate stress (g = -0.78), decrease anxiety (g = -1.14), mitigate depression (g = -0.96) and improve quality of life (g = 0.48). Positive psychology, mindfulness, cognitive behavioural therapy, acceptance and commitment-based intervention exhibited medium effects in strengthening resilience. Short-term effects of RRPIs on enhancing resilience were observed at 3-month follow-up period (g = 0.50). The incorporation of RRPIs into the management of patients with long-term disease shows a positive impact on their resilience, stress, anxiety, depression and quality of life. The results offer an evidence-based foundation for nurses in promoting resilience among patients with long-term disease.

A Noninferiority Trial Comparing 2 Days vs 5 Days of Terlipressin and Ceftriaxone in Terms of 5-Day Rebleeding for Patients With Acute Gastroesophageal Variceal Hemorrhage.

INTRODUCTION: This trial was to shorten the duration of both vasoconstrictors and prophylactic antibiotics to only 2 days in the therapy of acute gastroesophageal variceal hemorrhage. METHODS: After successful endoscopic hemostasis of gastroesophageal variceal hemorrhage, eligible patients were randomized to receive terlipressin infusion 1 mg per 6 hours and ceftriaxone 1 g daily for 5 days (group A) or a similar regimen for 2 days (group B). Primary end points were very early rebleeding at 5 days, and secondary end points included 48-hour hemostasis, 42-day rebleeding, and hospitalization days. RESULTS: Group A comprised 48 patients, and group B comprised 52 patients. Both groups were comparable in the severity of liver disease. Forty-eight-hour initial hemostasis was 95.8% in group A and 100% in group B ( P = 0.13). Very early rebleeding between 3 and 5 days occurred in 1 patient (2.1%) in group A and 2 patients (3.8%) in group B ( P = 0.60). The difference was 1.8% and the 95% confidence interval was -1.31% to 2.08%, which demonstrated noninferiority. Forty-two-day rebleeding occurred in 5 patients (10.4%) in group A and 4 patients (7.7%) in group B ( P = 0.63). The median hospitalization days were 8.5 ± 3.8 days in group A vs 5.6 ± 2.6 days in group B ( P < 0.001). DISCUSSION: After successful endoscopic hemostasis of acute variceal bleeding, combination of 2-day terlipressin infusion and ceftriaxone therapy was not inferior to the 5-day regimen in terms of very early rebleeding, with the advantage of shortening hospitalization stay.

Prevalence of swallowing disorder in different dementia subtypes among older adults: a meta-analysis.

BACKGROUND: Ageing process and abnormal protein accumulation in dementia damage neural pathways affecting the swallowing process and leading to swallowing disorder. OBJECTIVE: To estimate the prevalence of swallowing disorder among older adults with different dementia subtypes. METHODS: We conducted a systematic search across multiple databases, including PubMed, Embase, Scopus, Web of Science and OVID Medline. The meta-analysis employed R (version 4.0.2) and utilised a generalised linear mixed model with a random-effect approach to estimate the pooled prevalence of swallowing disorder among older adults, considering various dementia subtypes. The quality of included studies was assessed using Hoy's criteria. Heterogeneity was identified through Cochrane's Q and I2 statistics. To further explore heterogeneity, moderator analysis was performed to identify the contributing variables among the included studies. RESULTS: Eighteen studies with 12,532 older adults with different dementia subtypes were enrolled in our meta-analysis. The pooled prevalence of swallowing disorder among older adults with dementia was 58%, with 46.5% for Alzheimer's dementia, 34.9% for Parkinson's dementia, 18.8% for vascular dementia, 16.3% for mixed dementia and 12.2% for Lewy body dementia. According to assessment tools, Alzheimer's dementia had the highest prevalence, with 58% in instrumental assessments and 39% in clinical assessments. Medical history, Alzheimer's dementia, moderate-to-severe Clinical Dementia Rating, delayed oral phase, delayed pharyngeal phase and poor tongue motility contributed to the heterogeneity of the included studies. CONCLUSIONS: More than half of older adults with dementia demonstrate to have swallowing disorder. Our findings offer valuable insights to healthcare professionals for the identification of swallowing disorder in ageing population with dementia.

Hospital nurses perceived challenges and opportunities in the care of people with dementia: A mixed-methods systematic review.

AIM: To synthesise evidence from the literature on hospital nurses' perceived challenges and opportunities in the care of people with dementia. BACKGROUND: People with dementia often have longer lengths of hospital stay and poorer health outcomes compared to those without dementia. Nurses play a pivotal role in the care of people with dementia. However, there is a scarcity of systematic reviews that synthesise the challenges and opportunities they perceive. METHODS: A mixed-methods systematic review was conducted with a database search covering Ageline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Emcare, Embase, Medline, PsycINFO, ProQuest, Scopus and Web of Science in April 2022. In total, 27 articles that met the selection criteria were critically reviewed and included in this systematic review. Data from the selected articles were extracted and synthesised using a convergent segregated approach. RESULTS: Three main themes and eight subthemes were identified. Theme 1 described nurse-related factors consisting of the lack of capability in dementia care, experiencing multiple sources of stress and opportunities for nurses to improve dementia care. Theme 2 revealed people living with dementia-related factors including complex care needs and the need to engage family carers in care. Theme 3 explained organisation-related factors comprising the lack of organisational support for nurses and people with dementia and opportunities for quality dementia care. CONCLUSION: Hospital nurses experience multidimensional challenges in the care of people with dementia. Opportunities to overcome those challenges include organisational support for nurses to develop dementia care capability, reduce their stress and partner with the family caregivers. RELEVANCE TO CLINICAL PRACTICE: Hospitals will need to build an enabling environment for nurses to develop their capabilities in the care of people with dementia. Further research in empowering nurses and facilitating quality dementia care in acute care hospitals is needed. REPORTING METHOD: The review followed the PRISMA 2020 checklist. PATIENT OR PUBLIC CONTRIBUTION: No.