Mindfulness and loneliness in retired older adults in China: mediation effects of positive and negative affect.

Objectives: Drawing from the mindfulness framework and the broaden-and-build theory, this study investigates the extent to which mindfulness influences loneliness and whether the relation is mediated by positive and negative affect.Method: Data were collected from 748 retired older adults aged 60 and above in Chengdu, China in 2022. Loneliness and mindfulness were measured by the UCLA loneliness scale and by the short-form version of the Five Facet Mindfulness Questionnaire, while the positive and negative affect was assessed by the International Positive and Negative Affect Schedule.Results: The results of this study show that mindfulness was positively associated with positive affect (ß = 0.37, p<.001), negatively related to negative affect (ß=-0.21, p<.001) and loneliness (ß=-0.13, p<.001), and had an indirect effect on loneliness via positive and negative affect (ß=-0.20, p<.001).Conclusion: The findings suggest that mindfulness could be a positive resource for improving mental health and reducing loneliness among retired older adults in China.

FGF23 facilitates IL-1ß synthesis in rheumatoid arthritis through activating PI3K, Akt, and NF-κB pathways.

Rheumatoid arthritis (RA) is a well-known autoimmune disorder related with joint pain, joint swelling, cartilage and bone degradation as well as deformity. Fibroblast growth factor 23 (FGF23) is an endocrine factor of the FGF family primarily produced by osteocytes and osteoblasts, involves an essential effect in pathogenesis of RA. IL-1ß is a vital proinflammatory factor in the development of RA. However, the role of FGF23 on IL-1ß synthesis in RA has not been fully explored. Our analysis of database revealed higher levels of FGF23 and IL-1ß in RA samples compared with healthy controls. High-throughput screening demonstrated that IL-1ß is a potential candidate factor after FGF23 treatment in RA synovial fibroblasts (RASFs). FGF23 concentration dependently promotes IL-1ß synthesis in RASFs. FGF23 enhances IL-1ß expression by activating the PI3K, Akt, and NF-κB pathways. Our findings support the notion that FGF23 is a promising target in the remedy of RA.

Adaptive Autonomous Protocol for Secured Remote Healthcare Using Fully Homomorphic Encryption (AutoPro-RHC).

The outreach of healthcare services is a challenge to remote areas with affected populations. Fortunately, remote health monitoring (RHM) has improved the hospital service quality and has proved its sustainable growth. However, the absence of security may breach the health insurance portability and accountability act (HIPAA), which has an exclusive set of rules for the privacy of medical data. Therefore, the goal of this work is to design and implement the adaptive Autonomous Protocol (AutoPro) on the patient's remote healthcare (RHC) monitoring data for the hospital using fully homomorphic encryption (FHE). The aim is to perform adaptive autonomous FHE computations on recent RHM data for providing health status reporting and maintaining the confidentiality of every patient. The autonomous protocol works independently within the group of prime hospital servers without the dependency on the third-party system. The adaptiveness of the protocol modes is based on the patient's affected level of slight, medium, and severe cases. Related applications are given as glucose monitoring for diabetes, digital blood pressure for stroke, pulse oximeter for COVID-19, electrocardiogram (ECG) for cardiac arrest, etc. The design for this work consists of an autonomous protocol, hospital servers combining multiple prime/local hospitals, and an algorithm based on fast fully homomorphic encryption over the torus (TFHE) library with a ring-variant by the Gentry, Sahai, and Waters (GSW) scheme. The concrete-ML model used within this work is trained using an open heart disease dataset from the UCI machine learning repository. Preprocessing is performed to recover the lost and incomplete data in the dataset. The concrete-ML model is evaluated both on the workstation and cloud server. Also, the FHE protocol is implemented on the AWS cloud network with performance details. The advantages entail providing confidentiality to the patient's data/report while saving the travel and waiting time for the hospital services. The patient's data will be completely confidential and can receive emergency services immediately. The FHE results show that the highest accuracy is achieved by support vector classification (SVC) of 88% and linear regression (LR) of 86% with the area under curve (AUC) of 91% and 90%, respectively. Ultimately, the FHE-based protocol presents a novel system that is successfully demonstrated on the cloud network.

Environmental trade-offs and externalities of electrochemical-based batteries: Quantitative analysis between lithium-ion and vanadium redox flow units.

This study aims to increase the scientific knowledge of the environmental impacts and externalities of two promising electrochemical-based techniques for large-scale stationary energy storage: lithium nickel cobalt manganese (NCM) and vanadium redox flow (VRF) batteries. The global warming potential (GWP) and cumulative energy demand (CED) for NCM and VRF batteries are 28 kg CO2eq and 410 MJ and 186 kg CO2eq and 3080 MJ, respectively, for the provision of 1 MWh of electricity. While the trend of the environmental externality results is proportional to the environmental impact results, the environmental costs from GWP and terrestrial ecotoxicity impacts contribute the largest share of the total environmental costs for both batteries. Overall, NCM batteries have favorable environmental performance in terms of their impact values and externalities but still show relatively higher contributions in human toxicity and ozone layer depletion impacts, based on their high resource uses. The VRF batteries, on the other hand, report higher impacts in abiotic depletion, GWP and terrestrial ecotoxicity, mainly due to their great mass of the electrolyte. Our results highlight the importance of substituting the active metals with low-impact metals or carefully considering the origin of key materials while also taking advantage of the properties of the battery to carefully assess possible advancements in battery design. The environmental externality results also provide essential information for the future development of battery industries for stationary applications with energy and environmental benefits.

DPP4 reduces proinflammatory cytokine production in human rheumatoid arthritis synovial fibroblasts.

Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by increasing levels of proinflammatory cytokines. The ubiquitous enzyme dipeptidyl peptidase-4 (DPP4, also known as CD26) regulates different immune disorders, although the effects of DPP4 in RA are uncertain. Here, we found lower levels of DPP4 in RA synovial tissues compared with normal tissues. DPP4 levels were also lower in a rat collagen-induced arthritis model than in control (healthy) rats. Overexpression of DPP4 or exogenous treatment of RA synovial fibroblasts with DPP4 reduced levels of proinflammatory interleukin (IL)-1ß, IL-6, and IL-13, and increased anti-inflammatory IL-10 synthesis, while DPP4 inhibitors sitagliptin and vildagliptin increased proinflammatory cytokine production, indicating an enhanced risk of RA development. The evidence suggests that increasing DPP4 expression is a novel strategy for RA disease.

Improving parenting knowledge through caregiver education in China.

BACKGROUND: Caregivers' parenting knowledge is of importance to child development and to achieve positive child outcomes. Even though some caregiver education programs have demonstrated positive effects, most of them are carried out in developed countries and among western samples. As a developing country with the second-largest child population worldwide, China has initiated caregiver education programs to promote parenting knowledge among caregivers since 2016. This study examines the effect of an innovative caregiver education program on caregivers' perceived increase of parenting knowledge. METHODS: A total of 310 caregivers with a child aged between 0 and 3 from Z city, China, were randomly selected to complete a survey. Caregivers' perceived increase of parenting knowledge was assessed by five specified knowledge dimensions, namely, child growth, feeding behaviours, daily care, disease prevention and safety. The independent variable was program participation, measured by respondents' use of program services. OLS regression was employed to assess the association between caregivers' program participation and their perceived increase of knowledge, controlling basic demographic and socio-economic factors. RESULTS: In general, program participation had statistically significant associations with caregivers' perceived increase of parenting knowledge. The associations varied by service type. Particularly, online development evaluations and in-home sessions showed relatively consistent and positive effects on caregivers' perceived increase of parenting knowledge. CONCLUSIONS: This caregiver education program had a positive effect on caregivers' perceived increase of parenting knowledge, particularly through the use of the online development evaluations and in-home sessions. As one of the earliest initiatives of this kind in China, the findings reveal the promise of an innovative program to advance caregivers and children.

Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis.

The CCN family of matricellular proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1-2-3/CCN4-5-6) are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation. These proteins are well recognized for their important roles in many cellular processes, including cell proliferation, adhesion, migration and differentiation, as well as the regulation of extracellular matrix differentiation. Substantial evidence implicates four of the proteins (CCN1, CCN2, CCN3 and CCN4) in the inflammatory pathologies of rheumatoid arthritis (RA) and osteoarthritis (OA). A smaller evidence base supports the involvement of CCN5 and CCN6 in the development of these diseases. This review focuses on evidence providing insights into the involvement of the CCN family in RA and OA, as well as the potential of the CCN proteins as therapeutic targets in these diseases.

Melatonin Inhibits Osteoclastogenesis and Osteolytic Bone Metastasis: Implications for Osteoporosis.

Osteoblasts and osteoclasts are major cellular components in the bone microenvironment and they play a key role in the bone turnover cycle. Many risk factors interfere with this cycle and contribute to bone-wasting diseases that progressively destroy bone and markedly reduce quality of life. Melatonin (N-acetyl-5-methoxy-tryptamine) has demonstrated intriguing therapeutic potential in the bone microenvironment, with reported effects that include the regulation of bone metabolism, acceleration of osteoblastogenesis, inhibition of osteoclastogenesis and the induction of apoptosis in mature osteoclasts, as well as the suppression of osteolytic bone metastasis. This review aims to shed light on molecular and clinical evidence that points to possibilities of melatonin for the treatment of both osteoporosis and osteolytic bone metastasis. It appears that the therapeutic qualities of melatonin supplementation may enable existing antiresorptive osteoporotic drugs to treat osteolytic metastasis.

Adverse childhood experiences, mindfulness and happiness in Chinese college students during the COVID-19 pandemic.

The rise of literature on adverse childhood experiences (ACEs) has indicated a strong relationship between ACEs and negative life outcomes, leading to important implications for services to the population. However, less is known about the effects of ACEs on happiness and the role of mindfulness in this relation. This study examined the relationships between ACEs and happiness and whether mindfulness mediated the effects of ACEs on happiness in a sample of Chinese college students. The data were collected from 1871 college students from 12 colleges across China in September 2020. The findings of this study show that ACEs had significant negative effects on students' happiness and that mindfulness helped to substantially reduce the negative effects of ACEs on happiness. Students who experienced emotional neglect and abuse in childhood were affected the most. By contrast, this group is not the primary focus of mindfulness-based interventions in existing literature; thus, this study calls for specific mindfulness-based interventions for this vulnerable population.

S1P promotes IL-6 expression in osteoblasts through the PI3K, MEK/ERK and NF-κB signaling pathways.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks joint tissue. Interleukin (IL)-6 is a key proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we examined the effects of S1P on IL-6 expression in osteoblasts. Our results and records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-6 in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P increased mRNA and protein expression of IL-6. PI3K, MEK, ERK and NF-κB inhibitors and their small interfering RNAs (siRNAs) reduced S1P-promoted IL-6 expression. S1P also facilitated PI3K, MEK/ERK and NF-κB signaling cascades. Our results indicate that S1P promotes the expression of IL-6 in osteoblasts via the PI3K, MEK/ERK and NF-κB signaling pathways.

IMPLEMENTATION OF AN ELECTRONIC DASHBOARD WITH A REMOTE MANAGEMENT SYSTEM TO IMPROVE GLYCEMIC MANAGEMENT AMONG HOSPITALIZED ADULTS.

Objective: Better glycemic control for hospitalized diabetic patients significantly reduces health expenditures and improves disease outcomes. We developed a dynamic dashboard with a remote management system and evaluated its impact on inpatient glycemic control. Methods: This was an observational institution-wide study; study participants were enrolled from a 1,500-bed public medical center from 2016 to 2018. We evaluated the impact of a dynamic dashboard system, which analyzed and monitored all glucose data with virtual glycemic management recommendation by a team of endocrinologists, over 3 × 1-year periods: 2016 (pre-implementation), 2017 (development), and 2018 (implementation). Results: A total of 51,641 discharges with 878,159 blood glucose measurements were obtained during the 3-year period. After implementation of the dashboard system, the proportion of patients with poor glycemic control (hyperglycemia or hypoglycemia) was reduced by 31% (from 10.2 to 7.0 per day per 100 patients with glucose monitoring; P<.001); hyperglycemia decreased by 25% (from 6.1 to 4.6 per day per 100 patients with glucose monitoring; P<.001), and hypoglycemia decreased by 45% (from 4.2 to 2.3 per day per 100 patients with glucose monitoring; P<.001). Furthermore, the trend in the proportion of patients within the treat-to-target range showed significant improvement (P<.001) during the development period, with effectiveness maintained throughout the implementation period. Conclusion: We successfully installed a dynamic, electronic medical records-based dashboard monitoring system to improve inpatient glycemic control. The system, supported by a team of endocrinologists via remote recommendations, could efficiently fill an important need for improved glycemic management among hospitalized adults. Abbreviations: CDE = certified diabetes educator; DM = diabetes mellitus; EMR = electronic medical record; POC = point-of-care; TCVGH = Taichung Veterans General Hospital; UCSF = University of California, San Francisco; U.S. = United States; vGMS = virtual glucose management service.

S1P facilitates IL-1ß production in osteoblasts via the JAK and STAT3 signaling pathways.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)-1ß is a critical proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we investigated how S1P mediates IL-1ß expression in osteoblasts. Our analysis of records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-1ß in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P concentration dependently increased mRNA and protein expression of IL-1ß. Elevations in IL-1ß mRNA expression induced by S1P were reduced by the small interfering RNA (siRNA) against the S1P1 receptor. S1P also augmented JAK and STAT3 molecular cascades. We also found that JAK and STAT3 inhibitors and their siRNAs antagonized S1P-promoted IL-1ß expression. Our results indicate that S1P promotes the expression of IL-1ß in osteoblasts via the S1P1 receptor and the JAK and STAT3 signaling pathways.

Reconsidering the Role of Melatonin in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an inflammatory joint disorder characterized by synovial proliferation and inflammation, with eventual joint destruction if inadequately treated. Modern therapies approved for RA target the proinflammatory cytokines or Janus kinases that mediate the initiation and progression of the disease. However, these agents fail to benefit all patients with RA, and many lose therapeutic responsiveness over time. More effective or adjuvant treatments are needed. Melatonin has shown beneficial activity in several animal models and clinical trials of inflammatory autoimmune diseases, but the role of melatonin is controversial in RA. Some research suggests that melatonin enhances proinflammatory activities and thus promotes disease activity in RA, while other work has documented substantial anti-inflammatory and immunoregulatory properties of melatonin in preclinical models of arthritis. In addition, disturbance of the circadian rhythm is associated with RA development and melatonin has been found to affect clock gene expression in joints of RA. This review summarizes current understanding about the immunopathogenic characteristics of melatonin in RA disease. Comprehensive consideration is required by clinical rheumatologists to balance the contradictory effects.

Melatonin attenuates TNF-α and IL-1ß expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis.

The hormone melatonin has many properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose-dependently inhibits tumor necrosis factor-α (TNF-α) and interleukin (IL)-1ß expression through the PI3K/AKT, ERK, and NF-κB signaling pathways. We also identified that melatonin inhibits TNF-α and IL-1ß production by upregulating miR-3150a-3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast-like synoviocytes confirmed that the MT1 receptor is needed for the anti-inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen-induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF-α and IL-1ß production through downregulation of the PI3K/AKT, ERK, NF-κB signaling pathways, as well as miR-3150a-3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.

VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis.

Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; p = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; p = 0.01). Our findings suggest that VEGF-C gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the VEGF-C gene may be promising for RA treatment.

Patient-controlled analgesia for background pain of major burn injury.

BACKGROUND: Studies have suggested that intravenous patient-controlled analgesia (IV-PCA) can be used safely for the treatment of background pain in burn patients. However, no comprehensive protocols have been published. How patient or surgical factors correlate with the amount of opioid consumption remains unclear. The aim of this study is to provide an IV-PCA protocol for alleviating pain for burn injuries, and to assess factors correlated with opioid consumption. METHODS: At the Mackay Memorial Hospital, a retrospective analysis from June 27th to October 31st of 2015 was carried out to investigate the use of IV-PCA in relation to the demographic and clinical data of patients who suffered from burn injuries due to a massive explosion of flammable powder. A standardized morphine IV-PCA protocol with rapid escalation was implemented. Variables assessed included age, weight, gender, days of usage, total surface area burned (TBSAB) and operations. RESULTS: Among the 23 patients who received IV-PCA for burn pain control, it was noted that the larger the TBSAB and the higher the visual analogue scale (VAS), the more amount of morphine was consumed. Correlations between morphine consumption positively with weight (P < 0.01), female gender (P < 0.01), severity of injury (P = 0.01), and negatively with receiving operations (P = 0.01) were statistically significant. CONCLUSION: As the daily morphine consumption was positively correlated with TBSAB, VAS, weight, female gender, the use of our IV-PCA protocol was sufficient in the management of background pain for patients with major burn injury.

Associations between Adipokines in Arthritic Disease and Implications for Obesity.

Secretion from adipose tissue of adipokines or adipocytokines, comprising of bioactive peptides or proteins, immune molecules and inflammatory mediators, exert critical roles in inflammatory arthritis and obesity. This review considers the evidence generated over the last decade regarding the effects of several adipokines including leptin, adiponectin, visfatin, resistin, chemerin and apelin, in cartilage and bone homeostasis in the pathogenesis of rheumatoid arthritis and osteoarthritis, which has important implications for obesity.

Osteopontin inhibition of miR-129-3p enhances IL-17 expression and monocyte migration in rheumatoid arthritis.

BACKGROUND: Osteopontin (OPN) is an important proinflammatory cytokine in rheumatoid arthritis (RA). Levels of OPN have been shown to be significantly correlated with interleukin-17 (IL-17) production and expression of Th17 cells in the synovial fluid of RA patients. Here, we investigated the role of OPN in monocyte migration, IL-17 production and osteoblasts. METHODS: OPN and IL-17 expression profiles in osteoarthritis (OA) and RA synovial fluid were determined by enzyme-linked immunosorbent assay (ELISA). The expression of the microRNA, miR-129-3p, in osteoblasts was analyzed by real-time quantitative polymerase chain reaction (qPCR). Immunoreactive proteins were spotted by Western blotting. We used the collagen-induced arthritis (CIA) mouse model to investigate the role of OPN in monocyte migration during RA. RESULTS: OPN and IL-17 expression were higher in RA synovial fluid as compared to OA samples. We also found that OPN promotes IL-17 expression in osteoblasts and thereby enhances monocyte migration via the Syk/PI3K/Akt signaling pathway. miR-129-3p expression was found to be negatively regulated by OPN via the Syk/PI3K/Akt signal cascade. In contrast, lentiviral vectors expressing short hairpin RNA inhibited OPN expression and ameliorated articular swelling, cartilage erosion and monocyte infiltration in the ankle joints of CIA mice. CONCLUSION: To our knowledge, our study is the first to describe how OPN promotes monocyte migration by upregulating IL-17 expression in osteoblasts in RA disease. SIGNIFICANCE: These findings indicate that OPN could serve as a potential therapeutic target for the treatment of RA.

Prognostic significance of high-mobility group box protein 1 genetic polymorphisms in rheumatoid arthritis disease outcome.

Rheumatoid arthritis (RA) is a systemic inflammatory disease that causes chronic inflammation of the joints. Analysis of genetic variants offers promise for guiding treatment and improving outcomes in RA. High-mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein found in all mammal eukaryotic cells that participates in several biological functions including immune response, cell survival and apoptosis. We investigated the effects of HMGB1 gene polymorphisms on the risk of RA disease progression in a cohort of Chinese Han individuals. Four single nucleotide polymorphisms (SNPs) from the HMGB1 gene were selected and genotyped in 232 patients with RA and 353 healthy controls. We found that having one C allele in rs1360485 and one G allele in rs2249825 polymorphisms lowered the risk of RA in females. Moreover, among healthy controls, those who bore the C/G/T haplotype at SNPs rs1360485, rs2249825 and rs1412125 were at reduced risk of developing RA by 0.13-fold (p <0.05). This is the first report to examine the risk factors associated with HMGB1 SNPs in the development of RA disease in the Chinese Han population.

YKL-40-Induced Inhibition of miR-590-3p Promotes Interleukin-18 Expression and Angiogenesis of Endothelial Progenitor Cells.

YKL-40, also known as human cartilage glycoprotein-39 or chitinase-3-like-1, is a pro-inflammatory protein that is highly expressed in rheumatoid arthritis (RA) patients. Angiogenesis is a critical step in the pathogenesis of RA, promoting the infiltration of inflammatory cells into joints and providing oxygen and nutrients to RA pannus. In this study, we examined the effects of YKL-40 in the production of the pro-inflammatory cytokine interleukin-18 (IL-18), and the stimulation of angiogenesis and accumulation of osteoblasts. We observed that YKL-40 induces IL-18 production in osteoblasts and thereby stimulates angiogenesis of endothelial progenitor cells (EPCs). We found that this process occurs through the suppression of miR-590-3p via the focal adhesion kinase (FAK)/PI3K/Akt signaling pathway. YKL-40 inhibition reduced angiogenesis in in vivo models of angiogenesis: the chick embryo chorioallantoic membrane (CAM) and Matrigel plug models. We report that YKL-40 stimulates IL-18 expression in osteoblasts and facilitates EPC angiogenesis.