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Commentary on "Effect of gonadotropin-releasing hormone agonist treatment on near final height in girls with central precocious puberty and early puberty"
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Intrinsically Nonswellable Multifunctional Hydrogel with Dynamic Nanoconfinement Networks for Robust Tissue-Adaptable Bioelectronics
Full text linkDeveloping bioelectronics that retains their long-term functionalities in the human body during daily activities is a current critical issue. To accomplish this, robust tissue adaptability and biointerfacing of bioelectronics should be achieved. Hydrogels have emerged as promising materials for bioelectronics that can softly adapt to and interface with tissues. However, hydrogels lack toughness, requisite electrical properties, and fabrication methodologies. Additionally, the water-swellable property of hydrogels weakens their mechanical properties. In this work, an intrinsically nonswellable multifunctional hydrogel exhibiting tissue-like moduli ranging from 10 to 100 kPa, toughness (400-873 J m(-3)), stretchability (approximate to 1000% strain), and rapid self-healing ability (within 5 min), is developed. The incorporation of carboxyl- and hydroxyl-functionalized carbon nanotubes (fCNTs) ensures high conductivity of the hydrogel (approximate to 40 S m(-1)), which can be maintained and recovered even after stretching or rupture. After a simple chemical modification, the hydrogel shows tissue-adhesive properties (approximate to 50 kPa) against the target tissues. Moreover, the hydrogel can be 3D printed with a high resolution (approximate to 100 mu m) through heat treatment owing to its shear-thinning capacity, endowing it with fabrication versatility. The hydrogel is successfully applied to underwater electromyography (EMG) detection and ex vivo bladder expansion monitoring, demonstrating its potential for practical bioelectronics.ope
Assessment of Normal Systolic Blood Pressure Maintenance with the Risk of Coronary Artery Calcification Progression in Asymptomatic Metabolically Healthy Korean Adults with Normal Weight, Overweight, and Obesity
Full text linkMetabolically healthy obesity (MHO) is known to have a close association with subclinical coronary atherosclerosis. Despite recent data on the benefit of intensive systolic blood pressure (SBP) control in diverse clinical conditions, little is known regarding the association of normal SBP maintenance (SBPmaintain) with coronary artery calcification (CAC) progression in MHO. This study included 2724 asymptomatic adults (48.8 ± 7.8 years; 77.9% men) who had no metabolic abnormalities except overweight and obesity. Participants with normal weight (44.2%), overweight (31.6%), and obesity (24.2%) were divided into two groups: normal SBPmaintain (follow-up SBP < 120 mm Hg) and ≥elevated SBPmaintain (follow-up SBP ≥ 120 mm Hg). CAC progression was defined using the SQRT method, a difference of ≥2.5 between the square root (√) of the baseline and follow-up coronary artery calcium score. During a mean follow-up of 3.4 years, the proportion of normal SBPmaintain (76.2%, 65.2%, and 59.1%) and the incidence of CAC progression (15.0%, 21.3%, and 23.5%) was different in participants with normal weight, overweight, and obesity (all p < 0.05, respectively). The incidence of CAC progression was lower in the normal SBPmaintain group than in the ≥elevated SBPmaintain group in only participants with obesity (20.8% vs. 27.4%, p = 0.048). In multiple logistic models, compared to participants with normal weight, those with obesity had a higher risk of CAC progression. Normal SBPmaintain was independently associated with the decreased risk of CAC progression in participants with obesity. MHO had a significant association with CAC progression. Normal SBPmaintain reduced the risk of CAC progression in asymptomatic adults with MHO. © 2023 by the authors.ope
Schnurri-3 inhibition suppresses bone and joint damage in models of rheumatoid arthritis
No full textRheumatoid arthritis (RA) is a chronic inflammatory disease that leads to systemic and articular bone loss by activating bone resorption and suppressing bone formation. Despite current therapeutic agents, inflammation-induced bone loss in RA continues to be a significant clinical problem due to joint deformity and lack of articular and systemic bone repair. Here, we identify the suppressor of bone formation, Schnurri-3 (SHN3), as a potential target to prevent bone loss in RA. SHN3 expression in osteoblast-lineage cells is induced by proinflammatory cytokines. Germline deletion or conditional deletion of Shn3 in osteoblasts limits articular bone erosion and systemic bone loss in mouse models of RA. Similarly, silencing of SHN3 expression in these RA models using systemic delivery of a bone-targeting recombinant adenoassociated virus protects against inflammation-induced bone loss. In osteoblasts, TNF activates SHN3 via ERK MAPK-mediated phosphorylation and, in turn, phosphorylated SHN3 inhibits WNT/β-catenin signaling and up-regulates RANKL expression. Accordingly, knock-in of a mutation in Shn3 that fails to bind ERK MAPK promotes bone formation in mice overexpressing human TNF due to augmented WNT/β-catenin signaling. Remarkably, Shn3-deficient osteoblasts are not only resistant to TNF-induced suppression of osteogenesis, but also down-regulate osteoclast development. Collectively, these findings demonstrate SHN3 inhibition as a promising approach to limit bone loss and promote bone repair in RA.restrictio
Machine learning-based predictive models for the occurrence of behavioral and psychological symptoms of dementia: model development and validation
Full text linkThe behavioral and psychological symptoms of dementia (BPSD) are challenging aspects of dementia care. This study used machine learning models to predict the occurrence of BPSD among community-dwelling older adults with dementia. We included 187 older adults with dementia for model training and 35 older adults with dementia for external validation. Demographic and health data and premorbid personality traits were examined at the baseline, and actigraphy was utilized to monitor sleep and activity levels. A symptom diary tracked caregiver-perceived symptom triggers and the daily occurrence of 12 BPSD classified into seven subsyndromes. Several prediction models were also employed, including logistic regression, random forest, gradient boosting machine, and support vector machine. The random forest models revealed the highest area under the receiver operating characteristic curve (AUC) values for hyperactivity, euphoria/elation, and appetite and eating disorders; the gradient boosting machine models for psychotic and affective symptoms; and the support vector machine model showed the highest AUC. The gradient boosting machine model achieved the best performance in terms of average AUC scores across the seven subsyndromes. Caregiver-perceived triggers demonstrated higher feature importance values across the seven subsyndromes than other features. Our findings demonstrate the possibility of predicting BPSD using a machine learning approach.ope
A TEAD2-Driven Endothelial-Like Program Shapes Basal-Like Differentiation and Metastasis of Pancreatic Cancer
No full textBackground & Aims: Pancreatic ductal adenocarcinoma (PDA), with its highly metastatic propensity, is one of the most lethal subtypes of pancreatic cancer. Although recent large-scale transcriptomic studies have demonstrated that heterogeneous gene expressions play an essential role in determining molecular phenotypes of PDA, biological cues for and consequences of distinct transcriptional programs remain unclear.
Methods: We developed an experimental model that enforces the transition of PDA cells toward a basal-like subtype. We combined epigenome and transcriptome analyses with extensive in vitro and in vivo evaluations of tumorigenicity to demonstrate the validity of basal-like subtype differentiation in association with endothelial-like enhancer landscapes via TEA domain transcription factor 2 (TEAD2). Finally, we used loss-of-function experiments to investigate the importance of TEAD2 in regulating reprogrammed enhancer landscape and metastasis in basal-like PDA cells.
Results: Aggressive characteristics of the basal-like subtype are faithfully recapitulated in vitro and in vivo, demonstrating the physiological relevance of our model. Further, we showed that basal-like subtype PDA cells acquire a TEAD2-dependent proangiogenic enhancer landscape. Genetic and pharmacologic inhibitions of TEAD2 in basal-like subtype PDA cells impair their proangiogenic phenotypes in vitro and cancer progression in vivo. Last, we identify CD109 as a critical TEAD2 downstream mediator that maintains constitutively activated JAK-STAT signaling in basal-like PDA cells and tumors.
Conclusions: Our findings implicate a TEAD2-CD109-JAK/STAT axis in the basal-like differentiated pancreatic cancer cells and as a potential therapeutic vulnerability. © 2023 AGA Instituterestrictio
Association between polycythemia and risk of ischemic stroke in males based on the national health insurance service-health screening cohort
No full textBackground: Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor.
Research design and methods: This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models.
Results: In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20).
Conclusions: The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.restrictio
Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
Full text linkWe investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B-embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.ope
Systematic review and meta-analysis of randomization controlled and nonrandomized controlled studies on nurse-led nonpharmacological interventions to improve cognition in people with dementia
No full textAims and objectives: To evaluate nurse-led nonpharmacological interventions for improving cognition in people with dementia.
Background: Starting in 2006, donepezil was administered worldwide to improve cognition; however, its side effects limited its therapeutic value for long-term use, prompting a need for nonpharmacological interventions to improve cognition. Nurse-led nonpharmacological interventions are especially important because they are effective in terms of resources and costs, reduce patient latency and improve patient safety and satisfaction.
Methods: A systematic review was identified by searching 10 electronic databases. The search period was between 1 January 2007, and 30 September 2021. Languages were limited to English and Korean. The inclusion criteria were studies of nurse-led interventions that evaluated cognition using validated instruments. The exclusion criteria were qualitative research, scale development studies, abstracts and grey literature. Quality appraisal of research was conducted using the Risk of Bias in Nonrandomized Studies of Interventions for quasi-experimental studies and the Risk of Bias 2.0 for randomised controlled studies. This study was conducted in accordance with PRISMA reporting guideline (Appendix S1). The search protocol was registered in the PROSPERO (CRD 42021229358).
Results: A total of 24 studies were included in the systematic review, and 15 studies were included in the meta-analysis. Meta-analysis included 8 RCT and 7 quasi-experimental studies. The studies (11 quasi-experimental studies and 9 randomised controlled studies) demonstrated low to moderate quality of evidence for improving the cognition of people with dementia. The meta-analysis showed that nurse-led single nonpharmacological interventions more effectively improved cognition than complex interventions in people with dementia.
Conclusion: Nurse-led nonpharmacological interventions were effective for improving cognition in people with dementia.
Relevance to clinical practice: Nurses are qualified professionals with expertise in providing nonpharmacological interventions to improve cognition in people with dementia. Nurse-led nonpharmacological interventions for this purpose should be developed in future research.
Keywords: cognition; dementia; meta-analysis; nonpharmacological; nurse-led interventions.
© 2022 John Wiley & Sons Ltd.restrictio