Glycinamide Facilitates Nanocomplex Formation and Functions Synergistically with Bone Morphogenetic Protein 2 to Promote Osteoblast Differentiation In Vitro and Bone Regeneration in a Mouse Calvarial Defect Model.

BACKGROUND: This study aimed to identify glycine analogs conducive to the formation of cell-absorbable nanocomplexes, enhancing collagen synthesis and subsequent osteogenesis in combination with BMP2 for improved bone regeneration. METHODS: Glycine and its derivatives were assessed for their effects on osteogenic differentiation in MC3T3-E1 cells and human bone marrow mesenchymal stem cells (BMSCs) under osteogenic conditions or with BMP2. Osteogenic differentiation was assessed through alkaline phosphatase staining and real-time quantitative polymerase chain reaction (RT-qPCR). Nanocomplex formation was examined via scanning electron microscopy, circular dichroism, and ultraviolet-visible spectroscopy. In vivo osteogenic effects were validated using a mouse calvarial defect model, and bone regeneration was evaluated through micro-computed tomography and histomorphometric analysis. RESULTS: Glycine, glycine methyl ester, and glycinamide significantly enhanced collagen synthesis and ALP activity in conjunction with an osteogenic medium (OSM). GA emerged as the most effective inducer of osteoblast differentiation marker genes. Combining GA with BMP2 synergistically stimulated ALP activity and the expression of osteoblast markers in both cell lines. GA readily formed nanocomplexes, facilitating cellular uptake through strong electrostatic interactions. In an in vivo calvarial defect mouse model, the GA and BMP2 combination demonstrated enhanced bone volume, bone volume/tissue volume ratio, trabecular numbers, and mature bone formation compared to other combinations. CONCLUSION: GA and BMP2 synergistically promoted in vitro osteoblast differentiation and in vivo bone regeneration through nanocomplex formation. This combination holds therapeutic promise for individuals with bone defects, showcasing its potential for clinical intervention.

Predicting Smartphone Addiction Trajectories in Korean Adolescents: A Longitudinal Analysis of Protective and Risk Factors Based on a National Survey from 2018 to 2020.

This longitudinal study aimed to identify the role of psychosocial factors affecting smartphone addiction (SA) among Korean adolescents and predict the trajectory of SA based on the Korean Children and Youth Panel Survey (KCYPS) 2018 to 2020. The dependent variable is SA score as measured by the Korean Smartphone Addiction Propensity Scale (SAPS), and the independent variables are psychosocial factors (attention, grit, life satisfaction, self-esteem, aggression, depression, social withdrawal and physical symptom). Generalized estimating equation (GEE) analysis (adjusted for covariates) results indicated that attention (B = -0.346, P < .001), grit (B = -0.402, P < .001), life satisfaction (B = -0.150, P < .001), and self-esteem (B = -0.099, P < .001) were protective factors for reducing SA score. Conversely, aggression (B = 0.222, P < .001) and depression (B = 0.067, P = .005) were predicted to be risk factors for increasing SA score. A better understanding of the relationship between behavioral addiction and psychosocial development factors in adolescence will assist in the development of more effective prevention and treatment strategies.

The RIPK1 death domain restrains ZBP1- and TRIF-mediated cell death and inflammation.

RIPK1 is a multi-functional kinase that regulates cell death and inflammation and has been implicated in the pathogenesis of inflammatory diseases. RIPK1 acts in a kinase-dependent and kinase-independent manner to promote or suppress apoptosis and necroptosis, but the underlying mechanisms remain poorly understood. Here, we show that a mutation (R588E) disrupting the RIPK1 death domain (DD) caused perinatal lethality induced by ZBP1-mediated necroptosis. Additionally, these mice developed postnatal inflammatory pathology, which was mediated by necroptosis-independent TNFR1, TRADD, and TRIF signaling, partially requiring RIPK3. Our biochemical mechanistic studies revealed that ZBP1- and TRIF-mediated activation of RIPK3 required RIPK1 kinase activity in wild-type cells but not in Ripk1R588E/R588E cells, suggesting that DD-dependent oligomerization of RIPK1 and its interaction with FADD determine the mechanisms of RIPK3 activation by ZBP1 and TRIF. Collectively, these findings revealed a critical physiological role of DD-dependent RIPK1 signaling that is important for the regulation of tissue homeostasis and inflammation.

The Association between Social Support, Metabolic Syndrome, and Incidence of Cardio-Cerebrovascular Diseases in Older Adults: The ARIRANG Study.

PURPOSE: We investigated the association between social support, metabolic syndrome, and incident cardio-cerebrovascular disease (CCVD) in rural Koreans aged ≥50 years. MATERIALS AND METHODS: We conducted a prospective study using the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) dataset. From the baseline of 5169 adults, 1682 participants were finally included according to the exclusion criteria. For outcomes, myocardial infarction, angina, and stroke were included. For independent variables, the social support score and metabolic syndrome were used. Descriptive statistics and multivariate logistic regression were performed to investigate the association among the variables. Paired t-test was conducted to analyze the longitudinal variation of social support scores. RESULTS: During the 6.37 years of median follow-up, 137 participants developed CCVD. The adjusted odds ratio (aOR) of metabolic syndrome with persistently high social support was 2.175 [95% confidence interval (CI): 1.479-3.119]. The aOR of metabolic syndrome with persistently low social support was 2.494 (95% CI: 1.141-5.452). The longitudinal variation of the social support score of persistently high social support group was increased significantly by 4.26±26.32. The score of the persistently low social support group was decreased by 1.34±16.87 with no statistical significance. CONCLUSION: The presence of metabolic syndrome increases the likelihood of developing onset CCVD. Within the metabolic syndrome positive group, when social support was persistently low, the cohort developed more cardio-cerebrovascular disease compared to the persistently higher social support group. The social support score of the persistently low social support group could be improved through proper intervention. To prevent CCVD, metabolic syndrome components and low social support should be improved in the study participants.

Mitochondrial transplantation exhibits neuroprotective effects and improves behavioral deficits in an animal model of Parkinson's disease.

Mitochondria are essential organelles for cell survival that manage the cellular energy supply by producing ATP. Mitochondrial dysfunction is associated with various human diseases, including metabolic syndromes, aging, and neurodegenerative diseases. Among the diseases related to mitochondrial dysfunction, Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss and neuroinflammation. Recently, it was reported that mitochondrial transfer between cells occurred naturally and that exogenous mitochondrial transplantation was beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transfer on PD in vitro and in vivo. The results showed that PN-101 mitochondria isolated from human mesenchymal stem cells exhibited a neuroprotective effect against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine and rotenone in dopaminergic cells and ameliorated dopaminergic neuronal loss in the brains of C57BL/6J mice injected 30 â€‹mg/kg of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally. In addition, PN-101 exhibited anti-inflammatory effects by reducing the expression of pro-inflammatory cytokines in microglial cells and suppressing microglial activation in the striatum. Furthermore, intravenous mitochondrial treatment was associated with behavioral improvements during the pole test and rotarod test in the MPTP-induced PD mice. These dual effects of neuroprotection and anti-neuroinflammation support the potential for mitochondrial transplantation as a novel therapeutic strategy for PD.

Effect of NAMPT on the proliferation and apoptosis in odontoblast-like MDPC-23 cell.

This study aimed to evaluate the physiological role of NAMPT associated with MDPC-23 odontoblast cell proliferation. Cell viability was measured using the (DAPI) staining, caspase activation analysis and immunoblotting were performed. Visfatin promoted MDPC-23 odontoblast cell growth in a dose-dependent manner. Furthermore, the up-regulation of Visfatin promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers in MDPC-23 cells. However, FK-866 cell growth in a dose-dependent manner induced nuclear condensation and fragmentation. FK-866-treated cells showed H&E staining and increased apoptosis compared to control cells. The expression of anti-apoptotic factors components of the mitochondria-dependent intrinsic apoptotic pathway significantly decreased following FK-866 treatment. The expression of pro-apoptotic increased upon FK-866 treatment. In addition, FK-866 activated caspase-3 and PARP to induce cell death. In addition, after treating FK-866 for 72 h, the 3/7 activity of MDPC-23 cells increased in a concentration-dependent manner, and the IHC results also confirmed that Caspase-3 increased in a concentration-dependent. Therefore, the presence or absence of NAMPT expression in dentin cells was closely related to cell proliferation and formation of extracellular substrates.

An 8-Year Prospective, Observational, Multi-centre Post-Marketing Safety Surveillance Study Conducted in South Korea (2014-2022) Following the Introduction of GSK's Inactivated Quadrivalent Seasonal Influenza Vaccine (Fluarix Tetra) for Subjects Aged 6 Months and Older.

INTRODUCTION: Seasonal influenza is associated with substantial public health burden. The objective of this study was to assess the safety of inactivated quadrivalent seasonal influenza vaccine (IIV4, Fluarix Tetra, GSK, Belgium) in subjects aged ≥ 6 months in Korea. METHODS: This prospective, observational, non-comparative, multi-centre post-marketing surveillance study was conducted in Korea in subjects aged ≥ 3 years for 6 years (2014-2020) and extended to subjects aged 6-35 months for 4 years (2018-2022). Subjects received IIV4 in routine clinical practice according to local prescribing information. Adverse events (AEs) were recorded over 21 days post-vaccination. RESULTS: The group aged ≥ 3 years included 701 subjects (mean 31.97 years, range 3-86 years, 46.36% male), and the group aged 6-35 months included 687 subjects (mean 16.31 months, 47.02% male). In the group aged ≥ 3 years, 98 subjects (13.98%) reported 140 AEs, of which 42 events in 34 subjects (4.85%) were adverse reactions to vaccine (ARVs). Most of the ARVs were expected, mainly administration site reactions. There were seven mild unexpected ARVs. In the group aged 6-35 months, 248 AEs were reported in 149/687 subjects (21.69%). ARVs were reported in 25/687 subjects (3.64%, 29 events); one was considered unexpected. There were five serious AEs overall, none of which were considered related. CONCLUSION: No safety concerns were found during this surveillance study of IIV4 in subjects aged ≥ 6 months in Korea. The findings of this study suggest IIV4 is safe and well tolerated for use in all age groups with a vaccine indication.

Seasonal influenza is associated with over 5000 deaths annually in Korea, mainly in older adults. Annual vaccination is the most effective way of preventing seasonal influenza. The influenza virus strains in the vaccine are updated each year as the strains circulating change constantly. Monitoring of any unwanted medical incidents (adverse events) after vaccination is required to help assess vaccine safety. In this study, we monitored adverse events reported within 21 days of administration of Fluarix Tetra seasonal influenza vaccine (IIV4) in participants aged 6 months and older in Korea over a period of 4­6 years. Of the participants aged ≥ 3 years, 98 (14%) reported 140 adverse events, most commonly infections and infestations (most commonly nasopharyngitis such as the common cold), or general disorders and administration site conditions (most commonly pain or swelling at the injection site). In the participants aged 6­35 months, 149 (22%) reported 248 adverse events, also most commonly infections and infestations (such as the common cold) or general disorders and administration site conditions (most commonly fever or swelling at the injection site). There were five serious adverse events in total (adverse events that are life threatening or require hospitalization), but none of them were related to IIV4. In this study, we did not find any safety concerns for IIV4 in participants aged ≥ 6 months in Korea. The findings of this study suggest IIV4 is safe and well tolerated in all age groups with a vaccine indication.

A predictive model for medication adherence in older adults with heart failure.

AIMS: Although many studies have examined the predictors of medication adherence (MA), further empirical research is required to clarify the best model for predicting MA for older adults with heart failure (HF). Thus, we hypothesized a model in which information (knowledge), motivation (social support and depressive symptoms), and behavioural skills (barriers to self-efficacy) would be associated with MA in patients with HF. METHODS AND RESULTS: Using a cross-sectional survey, 153 adults aged ≥ 65 years taking medication for HF were recruited from a university hospital in Korea. Data were collected based on the information-motivation-behavioural skills (IMB) model constructs and MA. In the hypothesized path model, self-efficacy was directly related to MA (ß = -0.335, P = 0.006), whereas social support was indirectly related to MA through self-efficacy (ß = -0.078, P = 0.027). Depressive symptoms were directly related to MA (ß = 0.359, P = 0.004) and indirectly related to MA through self-efficacy (ß = 0.141, P = 0.004). The hypothesized MA model showed a good fit for the data. Knowledge, social support, and depressive symptoms accounted for 44.3% of the variance in self-efficacy (P = 0.004). Left ventricular ejection fraction, knowledge, social support, depressive symptoms, and self-efficacy explained 64.4% of the variance in MA (P = 0.004). CONCLUSION: These results confirmed the IMB model's suitability for predicting MA in older adults with HF. These findings may guide and inform intervention programmes designed to alleviate depressive symptoms in older adults with HF and enhance their HF knowledge, social support, and self-efficacy, with the ultimate goal of improving their MA.

Self-assembling biomolecules for biosensor applications.

Molecular self-assembly has received considerable attention in biomedical fields as a simple and effective method for developing biomolecular nanostructures. Self-assembled nanostructures can exhibit high binding affinity and selectivity by displaying multiple ligands/receptors on their surface. In addition, the use of supramolecular structure change upon binding is an intriguing approach to generate binding signal. Therefore, many self-assembled nanostructure-based biosensors have been developed over the past decades, using various biomolecules (e.g., peptides, DNA, RNA, lipids) and their combinations with non-biological substances. In this review, we provide an overview of recent developments in the design and fabrication of self-assembling biomolecules for biosensing. Furthermore, we discuss representative electrochemical biosensing platforms which convert the biochemical reactions of those biomolecules into electrical signals (e.g., voltage, ampere, potential difference, impedance) to contribute to detect targets. This paper also highlights the successful outcomes of self-assembling biomolecules in biosensor applications and discusses the challenges that this promising technology needs to overcome for more widespread use.

Case report: Ghost cell odontogenic carcinoma in a dog: diagnostics and surgical outcome.

A 6 year-old spayed female Poodle presented with a mandibular mass. Radiographic examination revealed osteolysis from the right mandibular canine to the fourth premolar, along with horizontal bone loss and dorsal displacement of the right mandibular first and second premolars. Skull cone beam computed tomography revealed osteolysis at the level of the right mandibular canine and fourth premolar. A destructive bone lesion was observed in the apical area of the right mandibular canine, with mass invasion of the interradicular bone of the right mandibular first molar near the mandibular canal. Consequently, unilateral total mandibulectomy and skin flap surgery were performed. Histopathological examination revealed poorly demarcated and infiltrative neoplastic epithelial cells that formed small islands and trabeculae. Neoplastic cells exhibited the malignant features of cytological atypia and high mitotic activity. Furthermore, the neoplastic epithelial cells frequently showed ghost cell changes and were diagnosed as ghost cell odontogenic carcinoma (GCOC). The dog was followed up for 1 year, during which no severe complications or local recurrence was observed, except for slight mandibular drift, tongue protrusion, and drooling. This case report describes the clinical features, diagnostic imaging, and histologic features of an unreported GCOC in a dog and the favorable outcome following surgical resection.

Radiation induces acute and subacute vascular regression in a three-dimensional microvasculature model.

Radiation treatment is one of the most frequently used therapies in patients with cancer, employed in approximately half of all patients. However, the use of radiation therapy is limited by acute or chronic adverse effects and the failure to consider the tumor microenvironment. Blood vessels substantially contribute to radiation responses in both normal and tumor tissues. The present study employed a three-dimensional (3D) microvasculature-on-a-chip that mimics physiological blood vessels to determine the effect of radiation on blood vessels. This model represents radiation-induced pathophysiological effects on blood vessels in terms of cellular damage and structural and functional changes. DNA double-strand breaks (DSBs), apoptosis, and cell viability indicate cellular damage. Radiation-induced damage leads to a reduction in vascular structures, such as vascular area, branch length, branch number, junction number, and branch diameter; this phenomenon occurs in the mature vascular network and during neovascularization. Additionally, vasculature regression was demonstrated by staining the basement membrane and microfilaments. Radiation exposure could increase the blockage and permeability of the vascular network, indicating that radiation alters the function of blood vessels. Radiation suppressed blood vessel recovery and induced a loss of angiogenic ability, resulting in a network of irradiated vessels that failed to recover, deteriorating gradually. These findings demonstrate that this model is valuable for assessing radiation-induced vascular dysfunction and acute and chronic effects and can potentially improve radiotherapy efficiency.

P. mirabilis-derived pore-forming haemolysin, HpmA drives intestinal alpha-synuclein aggregation in a mouse model of neurodegeneration.

BACKGROUND: Recent studies suggesting the importance of the gut-microbiome in intestinal aggregated alpha synuclein (α-syn) have led to the exploration of the possible role of the gut-brain axis in central nervous system degeneration. Proteus mirabilis (P. mirabilis), a gram-negative facultative anaerobic bacterium, has been linked to brain neurodegeneration in animal studies. We hypothesised that P. mirabilis-derived virulence factors aggregate intestinal α-synuclein and could prompt the pathogenesis of dopaminergic neurodegeneration in the brain. METHODS: We used vagotomised- and antibiotic-treated male murine models to determine the pathogenesis of P. mirabilis during brain neurodegeneration. The neurodegenerative factor that is driven by P. mirabilis was determined using genetically mutated P. mirabilis. The pathological functions and interactions of the virulence factors were determined in vitro. FINDINGS: The results showed that P. mirabilis-induced motor dysfunction and neurodegeneration are regulated by intestinal α-syn aggregation in vagotomised- or antibiotic-treated murine models. We deduced that the specific virulence factor, haemolysin A (HpmA), plays a role in the pathogenesis of P. mirabilis. HpmA is involved in α-synuclein oligomerisation and membrane pore formation, resulting in the activation of mTOR-mediated autophagy signalling in intestinal neuroendocrine cells. INTERPRETATION: Taken together, the results of the present study suggest that HpmA can interact with α-syn and act as a possible indicator of brain neurodegenerative diseases that are induced by P. mirabilis. FUNDING: This study was supported by a grant from the National Research Foundation of Korea.

Neuroprotective Effects of Water Extract from Brown Algae Petalonia binghamiae in an Experimental Model of Focal Cerebral Ischemia In Vitro and In Vivo.

Focal cerebral ischemia (fCI) can result in brain injury and sensorimotor deficits. Brown algae are currently garnering scientific attention as potential therapeutic candidates for fCI. This study investigated the therapeutic effects of the hot water extract of Petalonia binghamiae (wPB), a brown alga, in in vitro and in vivo models of fCI. The neuroprotective efficacy of wPB was evaluated in an in vitro excitotoxicity model established using HT-22 cells challenged with glutamate. Afterward, C57/BL6 mice were administered wPB for 7 days (10 or 100 mg/kg, intragastric) and subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) operation, which was used as an in vivo fCI model. wPB co-incubation significantly inhibited cell death, oxidative stress, and apoptosis, as well as stimulated the expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, and the nuclear translocation of its upstream regulator, nuclear factor erythroid 2-related factor 2 (Nrf2) in HT-22 cells challenged with glutamate-induced excitotoxicity. Pretreatment with either dose of wPB significantly attenuated infarction volume, neuronal death, and sensorimotor deficits in an in vivo fCI model. Furthermore, the attenuation of oxidative stress and apoptosis in the ischemic lesion accompanied the wPB-associated protection. This study suggests that wPB can counteract fCI via an antioxidative effect, upregulating the Nrf2/HO-1 pathway.

Effects of a self-determination theory-based physical activity programme for postmenopausal women with rheumatoid arthritis: A randomized controlled trial.

AIMS: The study aimed to develop and evaluate the effects of a self-determination theory-based, nurse-led, physical activity programme for postmenopausal women with rheumatoid arthritis. METHODS: Between December 2019 and April 2020, this randomized controlled trial recruited 62 postmenopausal women with rheumatoid arthritis from a university-affiliated hospital in South Korea. The intervention group participated in a self-determination theory-based, nurse-led, physical activity programme that consisted of Tai Chi-based physical activity, a supportive psychosocial strategy, and interactive counselling for 16 weeks, and the control group continued to undergo their usual care. RESULTS: There were statistically significant group-by-time interactions in physical activity and perceived sarcopenia, which favoured the intervention group. Additionally, the intervention group showed significant improvements in the perceived therapeutic efficacy of physical activity, grip strength, walking speed, disease activity score, and health-related quality of life. CONCLUSIONS: The programme developed in this study can be an effective and feasible approach for postmenopausal women with rheumatoid arthritis in improving physical activity, selected osteosarcopenic outcomes, and health-related quality of life. Further research is required to investigate the long-term effects of this theory-based programme for postmenopausal women in diverse settings.

Immunogenicity and Safety of a Newly Developed Live Attenuated Varicella Vaccine in Healthy Children: A Multi-National, Randomized, Double-Blinded, Active-Controlled, Phase 3 Study.

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 in healthy children to those of VarivaxTM (control). Children aged 12 months to 12 years were randomized in a ratio of 1:1 to receive either NBP608 or the control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. In total, 499 participants (NBP608, n = 251; control, n = 248) were enrolled. The seroconversion rate (SCR) measured using a FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for the SCR difference (NBP608 minus the control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of -15%. In an assessment using gpELISA, the SCR was 99.53% in the NBP608 group, and the 95% LCL for the SCR difference was 6.5%, which was higher than the specified non-inferiority margin of -15%. There were no significant differences between the NBP608 and control group with respect to the proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to VarivaxTM.

A Novel Multi-Component Formulation Reduces Inflammation In Vitro and Clinically Lessens the Symptoms of Chronic Eczematous Skin.

Long-term treatments for inflammatory skin diseases like atopic dermatitis or eczema can cause adverse effects. Super Protein Multifunction (SPM) was investigated as a potential treatment for managing skin inflammation by monitoring the expression of pro-inflammatory cytokines induced using LPS and poly(I:C)/TNFα in HaCaT keratinocytes and Hs27 fibroblasts as measured via RT-PCR. SPM solution was also assessed for its effect on cytokine release, measured using ELISA, in a UVB-irradiated 3D human skin model. To evaluate the efficiency of SPM, 20 patients with mild eczematous skin were randomized to receive SPM or vehicle twice a day for three weeks in a double-blind controlled trial. In vitro studies showed SPM inhibited inflammation-induced IL-1ß, IL-6, IL-33, IL-1α, TSLP, and TNFα expression or release. In the clinical study, the SPM group showed significant improvements in the IGA, PA, and DLQI scores compared to the vehicle group. Neither group showed significant differences in VAS (pruritus). Histological analysis showed reduced stratum corneum thickness and inflammatory cell infiltration. The results suggest that SPM may reduce inflammation in individuals with chronic eczematous skin.

A Historical Legacy for Universal Health Coverage in the Republic of Korea: Moving Towards Health Coverage and Financial Protection in Uganda Comment on "Health Coverage and Financial Protection in Uganda: A Political Economy Perspective".

Since 2001, when Uganda abolished user fees to improve the accessibility of healthcare, out-of-pocket costs still account for 42% of total health expenditure. Even if universal health coverage (UHC) is achieved on the demand-side, government authorities face political and economic challenges due to soaring burden of diseases. Therefore, this study aimed to re-analyze the implementation process according to three pillars by World Health Organization (WHO) based on Korean UHC-related articles. In terms of breadth, the national health insurance (NHI) in Korea UHC was established from 1977 for employees to 1989 for self-employed. In terms of depth, benefit packages in Korea UHC have expanded from essential medical services to expensive care (ultrasono, computerized tomography, etc) including benefit period. Finally, in terms of height of coverage, the government has tried to relieve financial burden of households with catastrophes and enhance benefit plan for major diseases till now. This historical legacy for UHC in Korea can pose lessons to policy-makers in developing countries including Uganda and Ghana.

Predicting physical activity and sarcopenia-related health outcomes in women with rheumatoid arthritis: A test of the self-determination theory.

AIM: This study aimed to examine a hypothetical model of physical activity (PA) and health outcomes related to sarcopenia in women with rheumatoid arthritis (RA) based on self-determination theory. DESIGN: Cross-sectional study. METHODS: This study included 214 women diagnosed with RA from the outpatient rheumatology department of a university-affiliated hospital in South Korea. Data were collected from September 2019 to August 2020 through structured questionnaires and anthropometric measurements and analysed using path analysis to test the hypothesized model. The primary health outcomes were perceived health status and sarcopenia-related health (thigh circumference, handgrip strength and sarcopenia risk). RESULTS: The final model's fit indices were adequate. Physical activity was directly affected by motivation for PA, while depression, self-efficacy for PA, health care provider's autonomy support and basic psychological needs satisfaction indirectly affected PA. Physical activity directly affected perceived health status and thigh circumference, while perceived sarcopenia risk and handgrip strength were directly affected by disease activity and age. PATIENT OR PUBLIC CONTRIBUTION: Patients were involved in a questionnaire-based survey.

The Effect of the Mechanical Properties of the 3D Printed Gelatin/Hyaluronic Acid Scaffolds on hMSCs Differentiation Towards Chondrogenesis.

BACKGROUND: Tissue engineering, including 3D bioprinting, holds great promise as a therapeutic tool for repairing cartilage defects. Mesenchymal stem cells have the potential to treat various fields due to their ability to differentiate into different cell types. The biomimetic substrate, such as scaffolds and hydrogels, is a crucial factor that affects cell behavior, and the mechanical properties of the substrate have been shown to impact differentiation during incubation. In this study, we examine the effect of the mechanical properties of the 3D printed scaffolds, made using different concentrations of cross-linker, on hMSCs differentiation towards chondrogenesis. METHODS: The 3D scaffold was fabricated using 3D bioprinting technology with gelatin/hyaluronic acid (HyA) biomaterial ink. Crosslinking was achieved by using different concentrations of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methlymorpholinium chloride n-hydrate (DMTMM), allowing for control of the scaffold's mechanical properties. The printability and stability were also evaluated based on the concentration of DMTMM used. The effects of the gelatin/HyA scaffold on chondrogenic differentiation was analyzed by utilizing various concentrations of DMTMM. RESULTS: The addition of HyA was found to improve the printability and stability of 3D printed gelatin/HyA scaffolds. The mechanical properties of the 3D gelatin/HyA scaffold could be regulated through the use of different concentrations of DMTMM cross-linker. In particular, the use of 0.25 mM DMTMM for crosslinking the 3D gelatin/HyA scaffold resulted in enhanced chondrocyte differentiation. CONCLUSION: The mechanical properties of 3D printed gelatin/HyA scaffolds cross-linked using various concentrations of DMTMM can influence the differentiation of hMSCs into chondrocytes.

Synergism Effect between Nanofibrillation and Interface Tuning on the Stiffness-Toughness Balance of Rubber-Toughened Polymer Nanocomposites: A Multiscale Analysis.

As the design and scalable technology development of tough, yet stiff, polymer nanocomposites receive attention in the automotive industry, fundamental understating of underlying toughening mechanisms at the nanoscale is inevitable. However, mechanical tests on rubber-toughened nanocomposites have shown that their overall fracture properties are significantly smaller than theoretical predictions. Our previous study showed that major factors in this regard are the simultaneous operation of different toughening mechanisms and the nanostructural features of the interface. As a result, it may be necessary to employ multiscale and multimechanism modeling strategies to accurately account for the contribution of each toughening mechanism. In this study, the effects of nanofibrillation (i.e., size, orientation, and dispersion) and interfacial tuning on the mechanical properties of nanofibrillated rubber-toughened nanocomposites are examined using molecular dynamics (MD) simulations. We report that by interfacial modification via grafting compatibilizer at the interface, nanofibrillated rubber-toughened polypropylene (PP) nanocomposite can achieve superior mechanical properties as a result of enhanced interfacial load transfer. Compared to pure ethylene propylene diene monomer rubber (EPDM)/PP system, an increase of 49% in energy absorbed per unit volume during fracture was achieved for 30% functionalized nanocomposites. Such an increase in energy dissipation was caused by a transition in the dominant crack propagation mechanism from interfacial slippage to crack-arresting behavior, owing to enhanced interfacial adhesion. MD simulations in conjunction with the multiscale model revealed that such a change in mechanism is caused by the formation of strong covalent bonds, interfacial friction, and the presence of a highly entangled polymeric network at the interface. Although the multiscale framework can be viewed as a road map for modeling the interface of various nanocomposite systems, the results obtained from our study may offer valuable insights for developing robust and scalable fabrication processes for nanofibrillated rubber-toughened nanocomposite structures, which pose significant technological challenges.