Adipose-derived stem cell modulate tolerogenic dendritic cell-induced T cell regulation is correlated with activation of Notch-NFκB signaling.

BACKGROUND: Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs. METHODS: Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs. RESULTS: Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway). CONCLUSIONS: ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application.

Late creation of vascular access increased post-hemodialysis mortality, hospitalization, and health-care expenditure: A population-based cohort study in Taiwan.

BACKGROUND/PURPOSE: The optimal timing of vascular access (VA) creation for hemodialysis (HD) and whether this timing affects mortality and health-care utilization after HD initiation remain unclear. Thus, we conducted a population-based study to explore their association. METHODS: We used Taiwan's National Health Insurance Research Database to analyze health-care outcomes and utilization in a cohort initiating HD during 2003-2013. We stratified patients by the following VA creation time points: >180, 91-180, 31-90, and ≤30 days before and ≤30 days after HD initiation and examined all-cause mortality, ambulatory care utilization/costs, hospital admission/costs, and total expenditure within 2 years after HD. Cox regression, Poisson regression, and general linear regression were used to analyze mortality, health-care utilization, and costs respectively. RESULTS: We identified 77,205 patients who started HD during 2003-2013. Compared with the patients undergoing VA surgery >180 days before HD initiation, those undergoing VA surgery ≤30 days before HD initiation had the highest mortality-15.92 deaths per 100-person-years, crude hazard ratio (HR) 1.56, and adjusted HR 1.28, the highest hospital admissions rates- 2.72 admission per person-year, crude rate ratio (RR) 1.48 and adjusted RR 1.32, and thus the highest health-care costs- US$31,390 per person-year, 7% increase of costs and 6% increase with adjustment within the 2-year follow-up after HD initiation. CONCLUSION: Late VA creation for HD can increase all-cause mortality, hospitalization, and health-care costs within 2 years after HD initiation. Early preparation of VA has the potential to reduce post-HD mortality and healthcare expenses for the ESKD patients.

The synergistic effect of full-spectrum light therapy and transient immunosuppressants prolonged allotransplant survival.

BACKGROUND: The lifelong administration of immunosuppressants remains its largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model. METHODS: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term anti-lymphocyte serum and cyclosporine-A. Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis. RESULTS: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared to the control (group 1). However, group 4 with FBLT combined with short-term ALS/CsA significantly prolonged median composite tissue allograft survival time (266 days) compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) (p<0.01). Group 4 also showed a significant increase in Treg cells (p = 0.04) and TGF-ß1 levels (p = 0.02), and a trend toward a decrease in IL-1ß levels (p = 0.03) at 16 weeks after transplantation as compared to control Group 1. CONCLUSIONS: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and anti-inflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival.

Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I2: 0% for retinal vein occlusion). CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42021267854.

Compare the effectiveness of extracorporeal shockwave and hyperbaric oxygen therapy on enhancing wound healing in a streptozotocin-induced diabetic rodent model.

Studies have revealed that both extracorporeal shock-wave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) can accelerate wound healing. This study aimed to compare the effectiveness of ESWT and HBOT in enhancing diabetic wound healing. A dorsal skin defect in a streptozotocin-induced diabetes rodent model was used. Postoperative wound healing was assessed once every 3 days. Histologic examination was performed with hematoxylin and eosin staining. Proliferation marker protein Ki-67 (Ki-67), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were evaluated with immunohistochemical (IHC) staining. The wound area was significantly reduced in the ESWT and HBOT groups compared to that in the diabetic controls. However, the wound healing time was significantly increased in the HBOT group compared to the ESWT group. Histological findings showed a statistical increase in neovascularization and suppression of the inflammatory response by both HBOT and ESWT compared to the controls. IHC staining revealed a significant increase in Ki-67, VEGF, and eNOS but suppressed 8-OHdG expression in the ESWT group compared to the HBOT group. ESWT facilitated diabetic wound healing more effectively than HBOT by suppressing the inflammatory response and enhancing cellular proliferation and neovascularization and tissue regeneration.

Ant Waist Surgery: Aesthetic Removal of Floating Ribs to Decrease the Waist-hip Ratio.

Decreasing waist circumference has become an essential feature in modern body contouring surgery owing to the attractiveness of hourglass body shapes. Traditionally, this can be achieved through lipomodeling and abdominal musculature strengthening techniques. An adjunctive procedure for ideal shaping of the waistline is resection of the 11th and 12th ribs, referred to as floating ribs. This study aimed to report and analyze clinical outcomes and self-reported patient satisfaction after "ant waist" surgery (floating rib removal) for aesthetic reasons. We retrospectively reviewed the medical records of five patients who had undergone bilateral 11th and 12th rib resections at a single institute in Taiwan in an outpatient setting. The mean lengths of the resected left and right 11th ribs were 9.1 and 9.5 cm, respectively. The mean lengths of the resected left and right 12th ribs were 6.3 and 6.4 cm, respectively. The mean waist-to-hip ratio decreased from 0.78 preoperatively to 0.72 postoperatively, with a mean decrease of 7.7%. No adverse events were reported. Generally, all patients reported being satisfied with the operation. Floating rib resection proved useful and effective in decreasing the waist-to-hip ratio using a safe, simple, and reproducible technique without significant complications. Although preliminarily, the authors' comprehensive demonstration of this ant waist surgery supports further studies focusing on waistline contouring.

Long-Term Complications and Patient-Reported Outcomes After Alloplastic Breast Reconstruction.

BACKGROUND: The most widely used method for breast reconstruction in Taiwan is alloplastic breast reconstruction, and traditionally, it can be categorized into immediate or delayed, single-stage or 2-stage procedures. We evaluated clinical outcomes and analyzed patients' self-reported satisfaction and quality of life after alloplastic breast reconstruction based on a previous preliminary study. PATIENT AND METHODS: The patients who underwent primary alloplastic breast reconstruction after mastectomy were recruited in 2006 to 2020 at a single institute in Taiwan. The assessment of clinical outcomes was conducted by retrospective chart review and risk analysis. The patients also completed the BREAST-Q, a condition-specific patient-reported outcome measure, at least 6 months after treatment. RESULTS: A total of 237 patients with 247 reconstructed breasts were enrolled in this study. The demographics showed that 205 (83%) were reconstructed using a 2-stage tissue expander-based procedure and 42 (17%) were 1-stage direct-to-implant reconstructions. The mean follow-up time was 79.5 months. The clinical assessment revealed that the overall complication rate was 34%, with infection being the most common (21 patients; 8%). According to risk analysis, smoking (odds ratio, 7.626; 95% confidence interval, 1.56-37.30; P = 0.012), and nipple-sparing mastectomy (odds ratio, 3.281; 95% confidence interval, 1.54-6.99; P = 0.002) were significant risk factors for overall complications. The questionnaire response rate was 38% (94 of 247), at least 6 months after treatment. The total mean score was 69.78. CONCLUSIONS: At a single institute in Taiwan from 2006 to 2020, alloplastic breast reconstruction, either single- or 2-stage, have acceptable complication rate and good postoperative satisfaction based on patient-reported outcomes. Both patient- and surgery-related factors presented as significant risk factors. Precise patient selection and comprehensive discussion between the patient and physician may play the important role to achieve optimal aesthetic outcomes.

Healthcare utilization and expenditure among individuals with end-stage kidney disease in Taiwan.

BACKGROUND/PURPOSE: The prevalence of end-stage kidney disease (ESKD) in Taiwan has been increasing in recent decades. ESKD care and medical expenditures constitute an important part of the entire healthcare system. METHODS: This study analyzed data collected from the National Health Insurance (NHI) Research Database from 2010 to 2018. RESULTS: The annual medical cost increased by approximately 4% both in the entire Taiwanese population and in its ESKD population. The total medical expenditure in the ESKD population from 2010 to 2018 increased from 48.03 to 65.65 billion reimbursement points, with dialysis treatments costing higher than non-dialysis treatments. ESKD outpatient and inpatient costs accounted for 10.4%-11.1% and 4.8%-5.6% of the entire NHI expenditure, respectively. The leading cause of inpatient costs was circulatory diseases, accounting for 29.3% of the total ESKD inpatient costs in 2018. Furthermore, percutaneous coronary intervention had the highest cost followed by simple percutaneous transluminal angioplasty. In 2018, the hemodialysis population had the highest average monthly cost of 73 thousand points per person, while the kidney transplant population had the lowest average monthly cost of 39 thousand points per person. CONCLUSION: Medical expenditure, including both inpatient and outpatient costs, of the ESKD population continued to grow from 2010 to 2018. The non-dialysis cost in the ESKD population was mainly for cardiovascular disease management and vascular access care, for which prevention will always be challenging.

Vessel Loop Shoelace Technique followed by Keystone Flap to Treat a Large Mid-back Defect.

The keystone design perforator island flap has been gaining popularity for reconstructing large cutaneous defects with sufficient soft tissue laxity. However, for a defect with insufficient local tissue and tense laxity such as upper to mid-back, a single keystone flap may not be so suitable for advancement and mobilization. Instead of an additional flap or double-opposite-designed keystone flaps, we attempted to apply the vessel loop shoelace technique for external expansion before proceeding with only one keystone flap reconstruction for a 15 × 15 cm skin and soft tissue defect on the mid-back. The outcome was a viable flap, with no ischemic flap edge, wound dehiscence, or infection. In our opinion, external expansion with vessel loops followed by a keystone flap might yield fairly good results for the reconstruction of mid-back defects; furthermore, this method may be ideal for defects located in regions lacking sufficient skin laxity.

Evaluation of air quality in Sunway City, Selangor, Malaysia from a mobile monitoring campaign using air pollution micro-sensors.

Due to the increase of the human population and the rapid industrial growth in the past few decades, air quality monitoring is essential to assess the pollutant levels of an area. However, monitoring air quality in a high-density area like Sunway City, Selangor, Malaysia is challenging due to the limitation of the local monitoring network. To establish a comprehensive data for air pollution in Sunway City, a mobile monitoring campaign was employed around the city area with a duration of approximately 6 months, from September 2018 to March 2019. Measurements of air pollutants such as carbon dioxide (CO2) and nitrogen dioxide (NO2) were performed by using mobile air pollution sensors facilitated with a GPS device. In order to acquire a more in-depth understanding on traffic-related air pollution, the measurement period was divided into two different time blocks, which were morning hours (8 a.m.-12 p.m.) and afternoon hours (3 p.m.-7 p.m.). The data set was analysed by splitting Sunway City into different zones and routes to differentiate the conditions of each region. Meteorological variables such as ambient temperature, relative humidity, and wind speed were studied in line with the pollutant concentrations. The air quality in Sunway City was then compared with various air quality standards such as Malaysian Air Quality Standards and World Health Organisation (WHO) guidelines to understand the risk of exposure to air pollution by the residence in Sunway City.

A comparison of the risk of congestive heart failure-related hospitalizations in patients receiving hemodialysis and peritoneal dialysis - A retrospective propensity score-matched study.

INTRODUCTION: Congestive heart failure (CHF) is associated with high mortality and a heavy financial and healthcare burden in the dialysis population. Determining which dialysis modality is associated with a higher risk of developing CHF might facilitate clinical decision making and surveillance programs in the dialysis population. METHODS: Using the Taiwan National Health Insurance Database, we recruited all incident dialysis patients during the period from January 1, 1998 to December 31, 2010. The propensity score matching method was applied to establish the matched hemodialysis (HD) and peritoneal dialysis (PD) cohort. Incidence rates and cumulative incidence rates of CHF-related hospitalization were first compared for the HD and PD patients. Multivariable subdistribution hazards models were then constructed to control for potential confounders. RESULTS: Among a total of 65,899 enrolled dialysis patients, 4,754 matched pairs of HD and PD patients were identified. The incidence rates of CHF in the matched HD and PD patients were 25.98 and 19.71 per 1000 patient-years, respectively (P = 0.001). The cumulative incidence rate of CHF was also higher in the matched HD patients (0.16, 95% confidence interval (CI)(0.12-0.21)] than in the corresponding PD patients (0.09, 95% CI [0.08-0.11])(P<0.0001). HD was consistently associated with an increased subdistribution hazard ratio (HR) of CHF compared with PD in the matched cohort (HR: 1.45, 95% CI [1.23-1.7]). Similar phenomenons were observed in either the subgroup analysis stratified by selected confounders or in the HD and PD group without matching. CONCLUSIONS: HD is associated with a higher risk of developing CHF-related hospitalization than PD. The surveillance program for CHF should differ in patients receiving different dialysis modalities.

Tunable Phospholipid Nanopatterns Mediated by Cholesterol with Sub-3 nm Domain Size.

The interactions between phospholipids and cholesterol have been extensively studied in the aqueous systems because of their vital functionalities in the cell membrane. In this study, instead of the self-assembly in water, we explored the microphase-separated structures of phospholipids in bulk and thin films in the absence of solvents and created a series of ordered nanostructures by incorporation of cholesterol into phospholipids. Three zwitterionic two-tailed phospholipids, that is, phosphatidylcholines (PCs), with different numbers of double bonds on the hydrocarbon tails were investigated, including egg PC, 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC), and 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC). We find that the nanostructures are highly dependent on the conformation of the tails on the PCs, which can be tailored by the number of double bonds on tails and the molar ratio of cholesterol to PC. By changing the molar ratio, egg PC with one double bond organizes into rich microdomains, including lamellae, spheres, and cylinders, whereas DOPC with two double bonds form spheres and cylinders and DPPC with no double bond forms lamellae only. The sizes of the microdomains are less than 3 nm, smaller than those of typical block copolymers. The biomolecule-based nanopatterns developed in this work provide a platform toward future applications of nanotechnology and biotechnology.

Atmospheric-pressure-plasma-jet processed carbon nanotube (CNT)-reduced graphene oxide (rGO) nanocomposites for gel-electrolyte supercapacitors.

This study evaluates DC-pulse nitrogen atmospheric-pressure-plasma-jet processed carbon nanotube (CNT)-reduced graphene oxide (rGO) nanocomposites for gel-electrolyte supercapacitor applications. X-ray photoelectron spectroscopy (XPS) indicates decreased oxygen content (mainly, C-O bonding content) after nitrogen APPJ processing owing to the oxidation and vaporization of ethyl cellulose. Nitrogen APPJ processing introduces nitrogen doping and improves the hydrophilicity of the CNT-rGO nanocomposites. Raman analysis indicates that nitrogen APPJ processing introduces defects and/or surface functional groups on the nanocomposites. The processed CNT-rGO nanocomposites on carbon cloth are applied to the electrodes of H2SO4-polyvinyl alcohol (PVA) gel-electrolyte supercapacitors. The best achieved specific (areal) capacitance is 93.1 F g-1 (9.1 mF cm-2) with 15 s APPJ-processed CNT-rGO nanocomposite electrodes, as evaluated by cyclic voltammetry under a potential scan rate of 2 mV s-1. The addition of rGOs in CNTs in the nanoporous electrodes improves the supercapacitor performance.